Archive for September, 2022

The discovery of a pig carcass on national forest land near Lake Koocanusa has prompted the Montana Department of Livestock, Montana Invasive Species Council, and USDA-APHIS Wildlife Services to hold public meetings about feral swine in Eureka and Libby on Thursday, Sept. 22.

The Libby meeting will be held at 1 p.m. in the Ponderosa Room at Libby City Hall.

While the carcass has not been confirmed as a feral pig, it has features often found in feral swine. The animal could also be a heritage breed of swine that looks similar.

The meetings will cover Montana laws restricting feral swine in the state, identifying signs and damage, and how to report sightings.

The Eureka meeting will be held at 6:30 p.m. at the Timbers Lodge (101 Julian Drive).

In August, the Department of Livestock received a report of a dead pig on Forest Service land west of Lake Koocanusa.

Canvassing of the area has failed to locate an owner of the animal. The investigation is ongoing, including genetic testing, but results wont be available for several weeks and may not be successful due to the decomposed state of the carcass.

Feral swine are an invasive species that pose a serious threat to Montanas agriculture, livestock, wildlife and landscapes.

Officials are asking the public to be on the lookout for feral swine or wild pigs and to report sightings to 406-444-2976.

While feral swine are not yet in Montana, we are aware of their expanding range in Canada and the risk of introduction through natural animal movement, escape of domestic animals, or deliberate release, said Tahnee Szymanski, Assistant State Veterinarian with the Department of Livestock, In coordination with our partners, we are working hard to prevent feral swine introduction.

For more information about feral swine and the Squeal on Pigs campaign go to squealonpigsmt.com.

For more information about these meetings contact the Montana Invasive Species Council at 406-444-0547.

The mission of the Montana Department of Livestock is to control and eradicate animal diseases, prevent the transmission of animal diseases to humans, and to protect the livestock industry from theft and predatory animals.

For more information on the Montana Department of Livestock, visit liv.mt.gov.

Original post:
Feral swine meetings Thursday in Eureka and Libby - The Western News

AGARWAL: How did decide on the treatment path you did?

Chowdhury: I have been involved in the TITAN study [NCT02489318] as one of the clinical chairs, so I have [vast] experience with apalutamide.1 We know that a significant subgroup in the TITAN study [benefited from therapy] and we know that that subgroup continued to show a benefit. This is a very reasonable treatment. The best evidence [from TITAN] supports apalutamide, and enzalutamide [Xtandi] is supported by the ARCHES study [NCT02677896], and both are very reasonable treatments.2 Certainly in my own practice, we have a lot of experience with apalutamide from TITAN for routine clinical practice. We also use the drug in nonmetastatic [castration-sensitive prostate cancer (CSPC) based on results from the phase 3 SPARTAN trial (NCT01946204)]. Doublets rather than ADT alone have been shown to produce a significant benefit, and sometimes we underestimate that. [This patient] has a poor prognosis and high-volume disease; he isnt someone with a super scan and a PSA level of several hundred ng/mL. Sometimes we can underestimate the disease and the lethality of disease in a man who has many years to live and is young.

Agarwal: How do you determine a treatment based on the available options for a certain patient?

Liaw: [The results of] multiple studies have shown us that moving some of the drugs that we once reserved for castration-resistant disease into the hormone-sensitive metastatic setting gives us a much more augmented long-term disease benefit in terms of disease control and overall survival [OS] benefit. I will talk to a patient who has high-volume disease about 4 options: docetaxel; apalutamide, such as what was done for this particular patient; abiraterone [Zytiga]; and enzalutamide. In someone who might have low-volume disease, sometimes theres a good discussion as to whether we do prostate radiation. In this case, he doesnt have a prostate anymore, so we wouldnt talk about that. But for de novo metastatic low-volume disease, you might think about that.

Often patients question how we choose among these 4 agents to use for systemic therapy, and no one necessarily has the right answer. Many times, it does come down to the patient themselves and their characteristics. In a patient like this who otherwise has an excellent performance status, is young, and has very few comorbidities, hes [a candidate] for all treatment options, vs some patients who might have more issues with steroid use, which would make things like abiraterone a bit harder for us to challenge them with. Patients who have hepatic or renal insufficiency might not be quite as good candidates for chemotherapy. One last thing that sometimes comes into the mix is cost issues with medications. For drugs like abiraterone which are off patent at this point, the price point might be more attractive, vs a drug like enzalutamide or apalutamide that is still branded.

Agarwal: How do you decide among the 4 options to treat prostate cancer?

Lowentritt: In 2019, apalutamide and enzalutamide got their approvals in the metastatic CSPC [mCSPC] space.3,4 Until then, only chemotherapy and abiraterone were available, and only 30% of people received abiraterone, so you still had the vast majority of people getting ADT alone. When I see my patients today and I talk to my partners and colleagues, its important to get to that first level of understanding that we need to intensify their therapy. Plenty of evidence shows that the standard of care [SOC] has long evolved past ADT alone. When Im talking to my patients now with a menu of offerings, I still do counsel them and encourage them. It is very clear that an oral option is often favored, although [in the future,] ways will evolve where theyre not necessarily mutually exclusive.

Abiraterone is still a wonderful medication because the exposure is a little bit longer in this part of the disease state, and patients will be on this for a longer period. Theres a slight concern about chronic steroid use in these patients. I dont know if that weighs heavier than the other concerns about chronic exposure to these medications on other systems in the body, but thats a component of it. Theres also a considerable cost-saving for patients who will be on drugs for a long time, so I definitely consider abiraterone as an excellent option. I have used both other options that are approved, apalutamide and enzalutamide, in this space, and there are differences. I tend to avoid enzalutamide in my elderly patients. My personal experience is there can be some increased level of problems with equilibrium or memory or just word finding for those patients over the long haul. I do think we have to recognize that this will be a longer course of therapy. Thankfully theyre all successful in extending life and having a long course, so I have these discussions [with my patients]. I try to do personal assessments, and there are some drug-drug interactions, although theyre minimal. Thyroid disease is more of a unique marker for apalutamide, but it generally occurs as small incidents and is easily managed. I have these discussions, but it ends up being a personal choice based on a lot of individual patient factors.

Agarwal: How do drug interactions play a role in your clinic? When do you decide to switch an anticoagulant rather than the prostate cancer treatment?

Liaw: In my personal practice, we do run into drug interactions here and there. It usually boils down to what options we have for anticoagulants and for treatment of prostate cancer. If their need for coagulation is a much more urgent issue, like in someone who has a saddle embolism, Im not touching their anticoagulant. Its more of an issue and is my bigger priority. For prostate cancer, if there are other equally suitable options and I can easily make a substitution, Im willing to do so if its a drug interaction issue. I dont come up against these tough decisions daily, but here and there we do have to make a decision to switch away from one drug to another.

Agarwal: When looking at the quality of life, why choose ADT plus apalutamide?

Chowdhury: For quality of life, we look at the studies, personal experiences, and at the patient in front of usand sometimes we underestimate how scary it is for a patient faced with metastatic disease. Patients like this want the best treatment. Sometimes because ADT works well, its an active treatment. Its among the most active treatments we have in solid tumor oncology. We focus on the current outlook rather than thinking about whats coming for the patient in a relatively short period of time. We see that [progression-free survival] on ADT alone is 12 to 18 months, and its shorter in terms of PSA, which obviously drives decision-making anxiety and treatment change. What I discuss with them are the data.

I honestly believe ADT is an elephant in the room. In the [United Kingdom], we underestimate toxicity to the detriment of our patients. Going forward, particularly in patients with lower-volume disease and good responses. Im hoping well see the escalation of therapy, particularly ADT, and get men on single-agent AR [androgen receptor] inhibitors, although that is not [an approved indication].

Something that weve talked about quite a lot in studies such as TITAN, ARCHES, and ARASEN [NCT02799602] is that PSA was blinded to patients and investigators.5 The benefit of PSA psychologically is massive for patients. When patients walk into our clinic room, one of the first, if not the first, question is about PSA. PSA is critical and PSA responsesthe depth, duration, and how that also ties in with the quality of lifeare important. For me, apalutamide and darolutamide [Nubeqa] are both good drugs. I chose apalutamide because of my experience in TITAN.

Agarwal: Why did you choose to use triplet therapy for this patient?

Liaw: In a case like this, we have many of the same options that we spoke about earlier in terms of doublet therapy. One thing to highlight is that this is a patient who has come in with de novo disease, which typically has a worse prognosis vs [a case where] metastatic recurrence has come back on the metachronous end. We want to put our best foot forward, so to speak. He is a 59-year-old patient who is otherwise independent with no medical issues, and he is also highly symptomatic. He has already had a pathologic fracture. His PSA numbers are tremendously elevated. Everything leads to not just high-volume disease, but many aspects of this disease that are high risk as well.

Data that support the use of triplet regimens like ADT, docetaxel, and abirateronea regimen that was championed in the PEACE-1 study [NCT01957436]and the backdrop of understanding the [benefit of] adding an additional layer of intensification to doublet combination therapy have led to success across all the different agents for mCSPC.6 [The PEACE-1] study looked to push that envelope a little bit further by adding on a third agent. We know that prostate cancer has some intrinsic heterogeneity. There will be some early clones that are more inherently insensitive or resistant to ADT, or maybe AR-directed therapy, through mechanisms such as AR variants or alterations. Trying to have something in the chemotherapy category as well as the AR-directed category, investigators hoped to show that a triplet regimen would elevate survival on top of just ADT plus docetaxel alone.

PEACE-1 has an interesting study design; it evolved as the SOC evolved. It was initially designed as a large randomized study to test whether the addition of abiraterone or radiation therapy, or the combination of both, to the SOC of ADT would benefit men with hormone-sensitive prostate cancer. However, [the SOC changed] as data from the CHAARTED trial [NCT00309985] and the STAMPEDE trial [NCT00268476] came out showing the additional benefits of docetaxel.7,8 [PEACE-1] laid out a prespecified statistical plan that provides for primary efficacy analysis of survival with the addition of abiraterone to the docetaxel-treated population. This study was very positive, but more to our point, the triplet regimen focused on the population of patients who got both ADT and docetaxel as part of the SOC. The addition of abiraterone demonstrated significant improvement in OS with a hazard ratio of 0.75 [95% CI, 0.59-0.95; P = .017]. This positive effect on OS was primarily pronounced in the patients with high-volume disease. The addition of abiraterone to hormonal therapy [must be] seriously considered because it is linked to a survival benefit.

Agarwal: As a urologist, how do you choose between doublet and triplet therapy?

Lowentritt: The latest data indicate that only about 3% of [patients] were getting docetaxel for metastatic hormone-sensitive disease. Its hard to call that the SOC, so you would love to see what the results are. My focus now is on intensifying therapy up front for these patients with high-volume disease who can tolerate it. Even in the ARCHES and TITAN trials, you had patients who had received docetaxel and then were put on oral therapy. [Patients enrolled were] usually in the low double digits or high single digits in those trials, but they did well and there were prespecified analyses to look at those that did equally well. [Some] data suggest that patients dont do worse when we combine [treatments].

Now, its about finding those patients whom my medical oncology colleagues will treat and the ones who will tolerate [treatment] well. Patients are [presenting at a] younger age, with better performance status, and they undergo a more intensified treatment up front due to high-volume disease. We are seeing this increased incidence of high-volume de novo disease, likely linked to decreased screening in the United States in the last 5 to 10 years. Regardless, we were seeing that trend even before then, and this disease seems to be getting worse. I do think itll be about finding those patients who fit the criteria and can go through [docetaxel plus oral therapy] together. We do not give cytotoxic chemotherapy in our practice; we give all the other types of therapies. Its about the patients having a good discussion with us and then making sure they have access to the medical oncologist, who can have a discussion with them and give them more details. Thats how I have approached it.

Agarwal: How is the process different if the patient has low-volume disease but is still de novo?

Liaw: PEACE-1 also included patients with low-volume disease, and it also tried to determine what type of [patient] benefited from the triplet regimen. As of the most recent data analysis, [we have no conclusive answers] in terms of OS benefit for these low-volume patients. Further longitudinal follow-up may change that, but right now, not a lot of strong evidence shows that patients with low-volume disease would necessarily benefit from a triplet regimen. Im generally not going to convince patients with low-volume disease to take 3 different therapies at the same time. Some exceptions to that [exist,] because when we define high-volume disease, were looking at the CHAARTED criteria, which are primarily focused on a [particular] number of lesions. It doesnt get at the heart of the matter, which is the overall volume of disease. One tiny, half-millimeter bone lesion still counts as a bone lesion in the CHAARTED trial. If you have a 10-centimeter lymph node thats obstructing kidney function, thats still 1 lesion. CHAARTED doesnt fully accommodate some well-known poor prognostic features of disease, such as a Gleason score or height of PSA [bounce].

There are some gray areas here, [such as if a patient] has low-volume disease and large, obstructive lymph nodes that dont quite meet high-volume disease criteria. If theyre highly symptomatic and they need an immediate response, I think theres still room to make a case for much more aggressive triplet therapy. Does that mean that its necessarily better over a doublet? I dont have those data. I dont know that well have great randomized prospective studies to be able to demonstrate this soon. Most likely, what well have to do is come together as a medical community to understand what the real-world data tell us, to help inform some of these decision-making processes. For patients with low-volume disease, Im still mostly thinking about doublet therapies.

Agarwal: How do you approach genomic profiling?

Chowdhury: [We have] both germline genomic profiling and somatic genomic profiling. From the somatic genomic profiling [perspective], its difficult because many patients [with homologous recombination repair gene alteration] from the PROfound study [NCT02987543] failed the FoundationOne testing.9 A lot of the samples had insufficient DNA extraction, so we need to think about that. When we have a patient with metastatic disease, particularly poor-prognosis metastatic disease, we need to be getting the DNA from those patients to check whether they have somatic mutations or germline mutations. Those are patients who will need options going forward, potentially like a PARP inhibitor.

From the germline side, the [National Comprehensive Cancer Network] guidelines are good. We dont have [enough] geneticist capacity in the [United Kingdom] for every high-risk localizedpatient. One must be a bit more pragmatic and look at particularly high-risk [ancestry] groups, such as Ashkenazi Jews [and others] with a significant history of likely BRCA-related cancers, and [consider] education around that. Its an evolving field. Tests are evolving, and not all genes are equal. BRCA1, BRCA2, and ATM are different genes with different actionability. Not all mutations are equal, so a homozygous deletion is different than a missense. And not all tests are equal. We must be careful about tests that [identify] mutations that just arent actionable. A lot of work [remains] to be done there. Its an interesting area, and you and your group demonstrated with olaparib [Lynparza] that there is actionability that can benefit patients. These are exciting times, but the data are early.

Lowentritt: [My center] was a trial site for PROfound, but I got 0 patients enrolled because all my samples failed. It informed how I then started doing testing, and I am now getting fresher biopsies at diagnosis. Im getting an initial somatic workup because the tissue is fresh. [Genetic testing] is more likely to be successful, and we have more [available samples] so that we can [determine results easier]. If a prostatectomy [has been done], that makes [genetic testing] easier as well. Most patients who were diagnosing with de novo metastatic disease are going to just have a biopsy. Im [receiving tissue samples] upfront with the understanding that many of these [mutations] are currently actionable. My approach now is to test early and test often. We have to recognize that most of the information that we currently know is helpful is available at the beginning. Future discovery will be based on resistance mechanisms and other things that are developing over time, so we can test as patients progress. I have gone to a lot more testing in the de novo setting.

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Recap: Recent Advances in the Treatment of Metastatic Castration-Sensitive Prostate Cancer - Cancer Network

Australia has a reputation for living well through our fortuitous supplies of mineral wealth in demand globally.

But in recent years a new breed of entrepreneur has moved the country into the future with developments in the fields of medical and information technology, green tech and biotech.

The companies range from those in the venture capital and development stage to operators listed on the stockmarket that make profits for shareholders.

Just how big the startup sector has become in recent years is highlighted by Paul Naphtali, co-founder and partner of venture fund Rampersand.

Back in 2013 the industry might have been investing $300 million a year, he said.

In 2021 that had jumped to $10 billion in Australia.

Editor of industry newsletter Biotech Daily David Langsam said the sector is moving to a more commercial footing.

Now 15 of the top 20 biotech companies have sales and revenue. They arent necessarily revenue positive but they do have commercial revenue. That wasnt the case 15 years ago, Langsam said.

That growth is reflecting itself on the sharemarkets where the Pharmaceuticals and Biotechnology index has risen 13 times since September 2006, while the All Ordinaries index is up only 1.38 times in the same period.

One new operator is Eugene Labs, which brings genetic testing into the home for a range of conditions and uses.

CEO Kunal Kalro, who co-founded the group with medical scientist Zoe Milgrom, said they are inspired by the belief that great health starts with your genetics.

To that end they provide people with seamless and actionable genomic health care.

Eugene Labs provides people with the means to do a range of genetic testing in the home so they avoid the difficulty and time cost of going to hospital unnecessarily.

One test they offer is called carrier screening.

Its a test that is either done pre-pregnancy or in early pregnancy that helps people understand their risk of having a child with a serious genetic condition, Mr Kalro said.

Once people are tested they can make decisions with the backing of their genetic and health professionals on how to prevent the passing on of genetic disorders, if that is possible.

If that is not possible then management of health and genetic issues can be planned.

There are also cancer and heart health tests available with everything done at home.

If people want to use Eugene Labs services they register on the internet for a saliva collection kit, fill in a detailed health survey online and send in their specimen for processing.

Eugene Labs sends these specimens to the appropriate labs for testing.

We are not a laboratory, Mr Kalro said.

However, It interpretS lab results into understandable language for its users.

Eugene Labs automated processes mean that instead of a clinic seeing 3000 people a year we can see 300,000 a year. That is because people do the testing at home.

The business began in 2019 and is still being funded by investors who want to support its fast, early stage growth.

We could reach profitability in 24 months, but we want to grow harder so we go out and raise more money to fund that, Mr Kalro said.

Another group in the medical field is Imugene, an ASX-listed company, which is developing a range of immunotherapy technologies that allow the body to track down and fight off cancer cells.

The companys most recent breakthrough is a treatment known as oncolytic virus therapy.

This involves a natural virus being genetically modified to enter cancer cells and replicate itself.

The virus kills cancer cells while avoiding damage to healthy cells. It means that the cancer is treated with very limited side effects for the patient undergoing treatment.

This treatment, along with some earlier developments, the company believes, can also help prime peoples immune systems against cancer, which will in turn make it more difficult for cancers to get to first base in the body.

Cancers being tested with the companys treatments include lung, pancreatic, colon and colorectal.

Testing is progressing, but the company is a long way from seeing cashflows.

In the June year just gone it lost $37.8 million, a reflection of the big spends on clinical trials and research necessary to bring new medical technologies to market.

But founder and executive chairman Paul Hopper described the company as in an enviable position financially with a long cash runway.

That means investors are still putting up cash to keep the wheels turning. It raised $95 million last financial year and another $80 million on September 9.

CEO Leslie Chong said the latest funding round will give ourselves an unimpeded runway to progress the numerous clinical trials that we have ongoing.

Eventually that will translate into shareholder value and improved patient outcomes, she said.

Although there are still people prepared to put up cash to fund the group, a shakeout in the biotech sector has hit it hard.

Imugene is currently valued at $1.5 billion on the stockmarket, but it was worth $2.5 billion a year ago.

See the rest here:
Australia moves to future in biotech and medical technologies with billions in new investment - The New Daily

Find out who can be a stem cell or bone marrow donor, and how to register.

A stem cell or bone marrow transplant is an important treatment for some people with types of blood cancer such as leukaemia, lymphoma and myeloma.

A transplant allows you to have high doses of chemotherapy and other treatments. The stem cellsare collected from the bloodstream or the bone marrow.Peoplehave a transplant either:

To be a donor you need to have stem cells that match the person you are donating to. To find this out, you have a blood test to look at HLA typing or tissue typing.

Staff in the laboratory look at the surface of your blood cells. They compare them to the surface of the blood cells of the person needing a transplant.

Everyone has their own set of proteins on the surface of their blood cells. The laboratory staff look for proteins called HLA markers and histocompatibility antigens. They check for 10 HLA markers. The result of this test shows how good the HLA match is between you and the person who needs the cells.

Abrother or sisteris most likely to be a match. There is a 1 in 4 chance of your cells matching.This is called a matched related donor (MRD) transplant.Anyone else in the family is unlikely to match. This can be very frustrating for relatives who are keen to help.

Sometimes if your cells are a half (50%) match, you might still be able to donate stem cells or bone marrow to a relative. This is called a haploidentical transplant.

You can't donate stem cells or bone marrow to your relative if you're not a match.

It's sometimes possible to get a match from someoneoutside of the family. This is calleda matched unrelated donor. To find a matched unrelated donor, it'susually necessary to search large numbers of people whose tissue type has been tested. So doctorssearch national and international registers to try to find a match for your relative.

Even if you can't donate to your relative, you might be ableto become a donor for someone else. You can do this by contacting one of the UK registers.

There are different donor registersin the UK.These work with each otherand with international registersto match donors with people who need stem cells. This helps doctors find donors for their patients as quickly as possiblefrom anywhere in the world.

Each registry has specific health criteriaand listmedical conditions that mightpreventyou from donating. Check their websitefor this information. Once registered, the organisation will contactyou if you are a match for someone who needs stem cells or bone marrow.

British Bone Marrow Registry (BBMR)

To register with the BBMR, you mustbe a blood donor. BBMR would like toregister those groups they are particularly short of ontheir register.This includes men between the ages of 17 and 40. And womenaged between 17 and 40 who are from Black, Asian, and minority ethnicities and mixed ethnicity backgrounds.

You have a blood test for tissue typing. Your details are kept on file until you are 60.

Anthony Nolan

You must be aged between 16 and 30 to register with Anthony Nolan. You have a cheek swab to test fortissue typing. Your details are kept on the register until you are 60.

Welsh Bone Marrow Donor Registry

You must be aged between 17 and 30 and your details are kept on the register until you are 60. You have a blood test for tissue typing.

DKMS

To register you must be aged between 17 and 55. You havea cheek swab for tissue typing. Your details stay on the register until your61st birthday.

This page is due for review. We will update this as soon as possible.

See more here:
Who can donate stem cells or bone marrow? - Cancer Research UK

Bone marrow is the spongy tissue inside some of the bones in the body, including the hip and thigh bones. Bone marrow contains immature cells called stem cells.

Many people with blood cancers, such as leukemia and lymphoma, sickle cell anemia, and other life threatening conditions rely on bone marrow or cord blood transplants to survive.

People need healthy bone marrow and blood cells to live. When a condition or disease affects bone marrow so that it can no longer function effectively, a marrow or cord blood transplant could be the best treatment option. For some people, it may be the only option.

This article looks at everything there is to know about bone marrow.

Bone marrow is soft, gelatinous tissue that fills the medullary cavities, or the centers of bones. The two types of bone marrow are red bone marrow, known as myeloid tissue, and yellow bone marrow, known as fatty tissue.

Both types of bone marrow are enriched with blood vessels and capillaries.

Bone marrow makes more than 220 billion new blood cells every day. Most blood cells in the body develop from cells in the bone marrow.

Bone marrow contains two types of stem cells: mesenchymal and hematopoietic.

Red bone marrow consists of a delicate, highly vascular fibrous tissue containing hematopoietic stem cells. These are blood-forming stem cells.

Yellow bone marrow contains mesenchymal stem cells, or marrow stromal cells. These produce fat, cartilage, and bone.

Stem cells are immature cells that can turn into a number of different types of cells.

Hematopoietic stem cells in the bone marrow give rise to two main types of cells: myeloid and lymphoid lineages. These include monocytes, macrophages, neutrophils, basophils, eosinophils, erythrocytes, dendritic cells, and megakaryocytes, or platelets, as well as T cells, B cells, and natural killer (NK) cells.

The different types of hematopoietic stem cells vary in their regenerative capacity and potency. They can be multipotent, oligopotent, or unipotent, depending on how many types of cells they can create.

Pluripotent hematopoietic stem cells have renewal and differentiation properties. They can reproduce another cell identical to themselves, and they can generate one or more subsets of more mature cells.

The process of developing different blood cells from these pluripotent stem cells is known as hematopoiesis. It is these stem cells that are needed in bone marrow transplants.

Stem cells constantly divide and produce new cells. Some new cells remain as stem cells, while others go through a series of maturing stages, as precursor or blast cells, before becoming formed, or mature, blood cells. Stem cells rapidly multiply to make millions of blood cells each day.

Blood cells have a limited life span. This is around 120 days for red blood cells. The body is constantly replacing them. The production of healthy stem cells is vital.

The blood vessels act as a barrier to prevent immature blood cells from leaving bone marrow.

Only mature blood cells contain the membrane proteins required to attach to and pass through the blood vessel endothelium. Hematopoietic stem cells can cross the bone marrow barrier, however. Healthcare professionals may harvest these from peripheral, or circulating, blood.

The blood-forming stem cells in red bone marrow can multiply and mature into three significant types of blood cells, each with its own job:

Once mature, these blood cells move from bone marrow into the bloodstream, where they perform important functions that keep the body alive and healthy.

Mesenchymal stem cells are present in the bone marrow cavity. They can differentiate into a number of stromal lineages, such as:

Red bone marrow produces all red blood cells and platelets and around 6070% of lymphocytes in human adults. Other lymphocytes begin life in red bone marrow and become fully formed in the lymphatic tissues, including the thymus, spleen, and lymph nodes.

Together with the liver and spleen, red bone marrow also plays a role in getting rid of old red blood cells.

Yellow bone marrow mainly acts as a store for fats. It helps provide sustenance and maintain the correct environment for the bone to function. However, under particular conditions such as with severe blood loss or during a fever yellow bone marrow may revert to red bone marrow.

Yellow bone marrow tends to be located in the central cavities of long bones and is generally surrounded by a layer of red bone marrow with long trabeculae (beam-like structures) within a sponge-like reticular framework.

Before birth but toward the end of fetal development, bone marrow first develops in the clavicle. It becomes active about 3 weeks later. Bone marrow takes over from the liver as the major hematopoietic organ at 3236 weeks gestation.

Bone marrow remains red until around the age of 7 years, as the need for new continuous blood formation is high. As the body ages, it gradually replaces the red bone marrow with yellow fat tissue. Adults have an average of about 2.6 kilograms (kg) (5.7 pounds) of bone marrow, about half of which is red.

In adults, the highest concentration of red bone marrow is in the bones of the vertebrae, hips (ilium), breastbone (sternum), ribs, and skull, as well as at the metaphyseal and epiphyseal ends of the long bones of the arm (humerus) and leg (femur and tibia).

All other cancellous, or spongy, bones and central cavities of the long bones are filled with yellow bone marrow.

Most red blood cells, platelets, and most white blood cells form in the red bone marrow. Yellow bone marrow produces fat, cartilage, and bone.

White blood cells survive from a few hours to a few days, platelets for about 10 days, and red blood cells for about 120 days. Bone marrow needs to replace these cells constantly, as each blood cell has a set life expectancy.

Certain conditions may trigger additional production of blood cells. This may happen when the oxygen content of body tissues is low, if there is loss of blood or anemia, or if the number of red blood cells decreases. If these things happen, the kidneys produce and release erythropoietin, which is a hormone that stimulates bone marrow to produce more red blood cells.

Bone marrow also produces and releases more white blood cells in response to infections and more platelets in response to bleeding. If a person experiences serious blood loss, yellow bone marrow can activate and transform into red bone marrow.

Healthy bone marrow is important for a range of systems and activities.

The circulatory system touches every organ and system in the body. It involves a number of different cells with a variety of functions. Red blood cells transport oxygen to cells and tissues, platelets travel in the blood to help clotting after injury, and white blood cells travel to sites of infection or injury.

Hemoglobin is the protein in red blood cells that gives them their color. It collects oxygen in the lungs, transports it in the red blood cells, and releases oxygen to tissues such as the heart, muscles, and brain. Hemoglobin also removes carbon dioxide (CO2), which is a waste product of respiration, and sends it back to the lungs for exhalation.

Iron is an important nutrient for human physiology. It combines with protein to make the hemoglobin in red blood cells and is essential for producing red blood cells (erythropoiesis). The body stores iron in the liver, spleen, and bone marrow. Most of the iron a person needs each day for making hemoglobin comes from the recycling of old red blood cells.

The production of red blood cells is called erythropoiesis. It takes about 7 days for a committed stem cell to mature into a fully functional red blood cell. As red blood cells age, they become less active and more fragile.

White blood cells called macrophages remove aging red cells in a process known as phagocytosis. The contents of these cells are released into the blood. The iron released in this process travels either to bone marrow for the production of new red blood cells or to the liver or other tissues for storage.

Typically, the body replaces around 1% of its total red blood cell count every day. In a healthy person, this means that the body produces around 200 billion red blood cells each day.

Bone marrow produces many types of white blood cells. These are necessary for a healthy immune system. They prevent and fight infections.

The main types of white blood cells, or leukocytes, are as follows.

Lymphocytes are produced in bone marrow. They make natural antibodies to fight infection due to viruses that enter the body through the nose, mouth, or another mucous membrane or through cuts and grazes. Specific cells recognize the presence of invaders (antigens) that enter the body and send a signal to other cells to attack them.

The number of lymphocytes increases in response to these invasions. There are two major types of lymphocytes: B and T lymphocytes.

Monocytes are produced in bone marrow. Mature monocytes have a life expectancy in the blood of only 38 hours, but when they move into the tissues, they mature into larger cells called macrophages.

Macrophages can survive in the tissues for long periods of time, where they engulf and destroy bacteria, some fungi, dead cells, and other material that is foreign to the body.

Granulocytes is the collective name given to three types of white blood cells: neutrophils, eosinophils, and basophils. The development of a granulocyte may take 2 weeks, but this time reduces when there is an increased threat, such as a bacterial infection.

Bone marrow stores a large reserve of mature granulocytes. For every granulocyte circulating in the blood, there may be 50100 cells waiting in the bone marrow to be released into the bloodstream. As a result, half the granulocytes in the bloodstream can be available to actively fight an infection in the body within 7 hours of it detecting one.

Once a granulocyte has left the blood, it does not usually return. A granulocyte may survive in the tissues for up to 45 days, depending on the conditions, but it can only survive for a few hours in circulating blood.

Neutrophils are the most common type of granulocyte. They can attack and destroy bacteria and viruses.

Eosinophils are involved in the fight against many types of parasitic infections and against the larvae of parasitic worms and other organisms. They are also involved in some allergic reactions.

Basophils are the least common of the white blood cells. They respond to various allergens that cause the release of histamines, heparin, and other substances.

Heparin is an anticoagulant. It prevents blood from clotting. Histamines are vasodilators that cause irritation and inflammation. Releasing these substances makes a pathogen more permeable and allows for white blood cells and proteins to enter the tissues to engage the pathogen.

The irritation and inflammation in tissues that allergens affect are parts of the reaction associated with hay fever, some forms of asthma, hives, and, in its most serious form, anaphylactic shock.

Bone marrow produces platelets in a process known as thrombopoiesis. Platelets are necessary for blood to coagulate and for clots to form in order to stop bleeding.

Sudden blood loss triggers platelet activity at the site of an injury or wound. Here, the platelets clump together and combine with other substances to form fibrin. Fibrin has a thread-like structure and forms an external scab or clot.

Platelet deficiency causes the body to bruise and bleed more easily. Blood may not clot well at an open wound, and there may be a higher risk of internal bleeding if the platelet count is very low.

The lymphatic system consists of lymphatic organs such as bone marrow, the tonsils, the thymus, the spleen, and lymph nodes.

All lymphocytes develop in bone marrow from immature cells called stem cells. Lymphocytes that mature in the thymus gland (behind the breastbone) are called T cells. Those that mature in bone marrow or the lymphatic organs are called B cells.

The immune system protects the body from disease. It kills unwanted microorganisms such as bacteria and viruses that may invade the body.

Small glands called lymph nodes are located throughout the body. Once lymphocytes are made in bone marrow, they travel to the lymph nodes. The lymphocytes can then travel between each node through lymphatic channels that meet at large drainage ducts that empty into a blood vessel. Lymphocytes enter the blood through these ducts.

Three major types of lymphocytes play an important part in the immune system: B lymphocytes, T lymphocytes, and NK cells.

These cells originate from hematopoietic stem cells in bone marrow in mammals.

B cells express B cell receptors on their surface. These allow the cell to attach to an antigen on the surface of an invading microbe or another antigenic agent.

For this reason, B cells are known as antigen-presenting cells, as they alert other cells of the immune system to the presence of an invading microbe.

B cells also secrete antibodies that attach to the surface of infection-causing microbes. These antibodies are Y-shaped, and each one is akin to a specialized lock into which a matching antigen key fits. Because of this, each Y-shaped antibody reacts to a different microbe, triggering a larger immune system response to fight infection.

In some circumstances, B cells erroneously identify healthy cells as being antigens that require an immune system response. This is the mechanism behind the development of autoimmune conditions such as multiple sclerosis, scleroderma, and type 1 diabetes.

These cells are so-called because they mature in the thymus, which is a small organ in the upper chest, just behind the sternum. (Some T cells mature in the tonsils.)

There are many different types of T cells, and they perform a range of functions as part of adaptive cell-mediated immunity. T cells help B cells make antibodies against invading bacteria, viruses, or other microbes.

Unlike B cells, some T cells engulf and destroy pathogens directly after binding to the antigen on the surface of the microbe.

NK T cells, not to be confused with NK cells of the innate immune system, bridge the adaptive and innate immune systems. NK T cells recognize antigens presented in a different way from many other antigens, and they can perform the functions of T helper cells and cytotoxic T cells. They can also recognize and eliminate some tumor cells.

These are a type of lymphocyte that directly attack cells that a virus has infected.

A bone marrow transplant is useful for various reasons. For example:

Stem cells mainly occur in four places:

Stem cells for transplantation are obtainable from any of these except the fetus.

Hematopoietic stem cell transplantation (HSCT) involves the intravenous (IV) infusion of stem cells collected from bone marrow, peripheral blood, or umbilical cord blood.

This is useful for reestablishing hematopoietic function in people whose bone marrow or immune system is damaged or defective.

Worldwide, more than 50,000 first HSCT procedures, 28,000 autologous transplantation procedures, and 21,000 allogeneic transplantation procedures take place every year. This is according to a 2015 report by the Worldwide Network for Blood and Marrow Transplantation.

This number continues to increase by over 7% annually. Reductions in organ damage, infection, and severe, acute graft-versus-host disease (GVHD) seem to be contributing to improved outcomes.

In a study of 854 people who survived at least 2 years after autologous HSCT for hematologic malignancy, 68.8% were still alive 10 years after transplantation.

Bone marrow transplants are the leading treatment option for conditions that threaten bone marrows ability to function, such as leukemia.

A transplant can help rebuild the bodys capacity to produce blood cells and bring their numbers to acceptable levels. Conditions that may be treatable with a bone marrow transplant include both cancerous and noncancerous diseases.

Cancerous diseases may or may not specifically involve blood cells, but cancer treatment can destroy the bodys ability to manufacture new blood cells.

A person with cancer usually undergoes chemotherapy before transplantation. This eliminates the compromised marrow.

A healthcare professional then harvests the bone marrow of a matching donor which, in many cases, is a close family member and ready it for transplant.

Types of bone marrow transplant include:

A persons tissue type is defined as the type of HLA they have on the surface of most of the cells in their body. HLA is a protein, or marker, that the body uses to help it determine whether or not the cell belongs to the body.

To check if the tissue type is compatible, doctors assess how many proteins match on the surface of the donors and recipients blood cells. There are millions of different tissue types, but some are more common than others.

Tissue type is inherited, and types pass on from each parent. This means that a relative is more likely to have a matching tissue type.

However, if it is not possible to find a suitable bone marrow donor among family members, healthcare professionals try to find someone with a compatible tissue type on the bone marrow donor register.

Healthcare professionals perform several tests before a bone marrow transplant to identify any potential problems.

These tests include:

In addition, a person needs a complete dental exam before a bone marrow transplant to reduce the risk of infection. Other precautions to lower the risk of infection are also necessary before the transplant.

Bone marrow is obtainable for examination by bone marrow biopsy and bone marrow aspiration.

Bone marrow harvesting has become a relatively routine procedure. Healthcare professionals generally aspirate it from the posterior iliac crests while the donor is under either regional or general anesthesia.

Healthcare professionals can also take it from the sternum or from the upper tibia in children, as it still contains a substantial amount of red bone marrow.

To do so, they insert a needle into the bone, usually in the hip, and withdraw some bone marrow. They then freeze and store this bone marrow.

National Marrow Donor Program (NMDP) guidelines limit the volume of removable bone marrow to 20 milliliters (ml) per kg of donor weight. A dose of 1 x 103 and 2 x 108 marrow mononuclear cells per kg is necessary to establish engraftment in autologous and allogeneic marrow transplants, respectively.

Complications related to bone marrow harvesting are rare. When they do occur, they typically involve problems related to anesthetics, infection, and bleeding.

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Home Blog Bone Marrow Stem Cell Dose Matters in Knee Osteoarthritis

If theres one overarching theme in orthobiologics that I have been discussing for almost two decades, its that measuring and delivering higher doses are critical for success. Despite this, 99% of physicians who offer these procedures dont know what dose theyre delivering and use bedside kits that can only achieve low doses. Today well go into our most recent publication that shows that the stem cell dose in bone marrow concentrate is directly tied to clinical outcomes in knee arthritis patients. Lets dig in.

Our study looked at the number of colony-forming mesenchymal stem cells (CFU-fs) in bone marrow concentrate (BMC) in knee arthritis patients and then the clinical outcome of the procedure (1). We found that those patients who had more stem cells in their BMC reported better outcomes. That fits with data published by others on BMC treatments in bone disease and low back degenerative disc disease (2,3).

While this may seem like a mundane finding, its the first of its kind in BMC used for knee osteoarthritis treatment. More importantly, it highlights how important dose is in these treatments and how many BMC treatments being delivered are likely under-dosing patients. Lets dive deeper into that concept.

77 clinic locations offering non-surgical Regenexx solutions for musculoskeletal pain.

77 clinic locations offering non-surgical Regenexx solutions for musculoskeletal pain.

Youre a doctor who just started dipping his toe into the waters of this new field called orthobiologics. You buy a simple bedside kit to produce PRP because its super easy without much commitment. You then at some point add in bone marrow concentrate through the same system with a different kit. Your world is easy and simple, as all your staff needs to know is where to put the kit in the machine and where the On button is located.

However, what you begin to realize after a few years is that all of this simplicity comes at a steep price. For example, you have no idea of the dose of orthobiologic youre delivering. At its most basic, everything else in medicine is tied to a dose, so this seems wrong. In addition, independent research shows that the dose that your simple machine is capable of delivering is low and that higher doses are tied to better outcomes. Hence, at some point, it hits you like one of those clown pies in the face, youve traded simplicity for your staff for poorer patient outcomes.

PRP (Platelet-Rich Plasma) and BMC (Bone Marrow Concentrate) are autologous procedures where the dose of platelets or cells varies widely from patient to patient. This is based on many factors including:

There are other factors that also influence outcomes like where this stuff is injected and how, but today well focus only on how the dose of whats injected can dramatically change how the patient responds.

The machine the doctor buys to produce PRP and BMC matters. The problem is that this decision is often based on a relationship with a sales rep and not the concept of dose as were discussing here. Lets dig in.

Ive blogged a few times on researchers who recently published big and well-done studies, but that used commercial kits that claim to produce PRP, but instead only produce plasma which has fewer than 2 times concentrated platelets (the minimum needed to call the product PRP). These kits are are Arthrex ACP and RegenLab (7). Hence, if you were a doctor who happened to purchase one of these systems and are using this stuff, you think youre delivering PRP, but youre not.

The vast majority of machines produce low-dose PRP at a 3-5X concentration. The good news is that if youre treating young patients this is fine, but as our long-standing research on mesenchymal stem cells in culture and published work on tenocyte healing shows, for older patients this concentration represents a severe under-dose (8). Meaning that if youre middle-aged or older, the higher the dose the better, because your older cells (unlike young ones) will respond to the extra platelets. Given that this is a direct dose-response relationship in these patients, your dose cant be too high in this age group.

High-dose PRP is 7-14X with most older patients needing 10-14X or higher. Few machines can achieve this and all have trade-offs. Take the Arthrex Angel device, which can produce high-dose PRP, but at a price. Rather than producing the more commonly used leukocyte-poor PRP (LP), this machine concentrates white blood cells with platelets, so instead you get bloody and leukocyte-rich PRP (LR). Or other machines that use an off-label double spin technique where the doctor uses the same kit twice. These machines like Emcyte can get to higher concentrations, but as we have seen testing this machine in our lab, the double spin can cause the platelets to clump, distributing them unevenly in the PRP. In addition, no research or FDA clearance is available on using the kit twice, so the reliability of that double spin product is unknown.

Weve never used any of these machines because we can produce any concentration of PRP in the lab that the doctor requires and make it leukocyte poor or rich. We can also produce it from peripheral blood or a bone marrow draw if thats already being done. Whats the downside? This approach takes a bigger commitment from the practice, meaning they have to be all in on orthobiologics.

For BMC, we have seen similar issues with bedside machines. Meaning as we have tested these machines in our lab, their ability to concentrate and get the most stem cells in the smallest volume is limited. The biggest issue is the simple lack of flexibility of the input volume and a higher output volume. What does that mean?

In trying to maximize the number of stem cells in a BMC sample, you first need to be able to increase the volume of high-quality marrow aspirate taken from the patient. That starts with taking a small volume of marrow aspirate from many sites, which maximizes the number of stem cells in the sample (2-4). Regrettably, we still see physicians short-changing patients by taking one large marrow pull from the patient, which dramatically reduces the number of stem cells taken from the patient.

Next, you need the flexibility to increase the marrow aspirate volume based on the age of the patient and the number of areas treated. For example, in an older patient who may have fewer stem cells per ml of BMA, just take more BMA to compensate. This really cant happen with bedside centrifuge kits, as they have a fixed input volume. That means that you only get one option on how much marrow can be processed. Compare that to a flexible lab-based system where you easily increase the volume processed to compensate for the clinical scenario.

Finally, the output volume is critical as well. Meaning, that if you take more BMA to get more stem cells, thats useless if your system gives you a single large volume of BMC to inject. Instead, you need the highest concentration possible from your large volume and that means that the system youre using puts all of those cells in the smallest possible volume. As an example, using a lab-based system, we often take 120 ml of BMA and get that down to 3-5 ml of BMC.

Once you leave the orthobiologic training wheels behind and get a significant number of treated patients completed, whats next? Based on the existing and emerging research, thats making sure that you can deliver the highestPRP and BMC dose possible. That means leaving the bedside kit world and transitioning to a lab. No company on earth has more experience than Regenexx helping providers graduate to a flexible lab platform safely and efficiently with strict SOPs and controls.

The upshot? Dose matters. The research continues to show that the providers who can maximize the dose of platelets and stem cells are likely getting better results than those who have maximized their convenience by using limited bedside kits. Is your practice ready for an upgrade? Is it time to leave the orthobiologic training wheels behind? If so, we got you covered.

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References:

(1) Centeno CJ, Berger DR, Money BT, Dodson E, Urbanek CW, Steinmetz NJ. Percutaneous autologous bone marrow concentrate for knee osteoarthritis: patient-reported outcomes and progenitor cell content. Int Orthop. 2022 Aug 6. doi: 10.1007/s00264-022-05524-9. Epub ahead of print. PMID: 35932306.

(2)Pettine KA, Murphy MB, Suzuki RK, Sand TT. Percutaneous injection of autologous bone marrow concentrate cells significantly reduces lumbar discogenic pain through 12 months. Stem Cells. 2015 Jan;33(1):146-56. doi: 10.1002/stem.1845. PMID: 25187512.

(3) Hernigou P, Beaujean F. Treatment of osteonecrosis with autologous bone marrow grafting. Clin Orthop Relat Res. 2002 Dec;(405):14-23. doi: 10.1097/00003086-200212000-00003. PMID: 12461352.

(4) Batini D, Marusi M, Pavleti Z, Bogdani V, Uzarevi B, Nemet D, Labar B. Relationship between differing volumes of bone marrow aspirates and their cellular composition. Bone Marrow Transplant. 1990 Aug;6(2):103-7. PMID: 2207448.

(5) Muschler GF, Boehm C, Easley K. Aspiration to obtain osteoblast progenitor cells from human bone marrow: the influence of aspiration volume. J Bone Joint Surg Am. 1997 Nov;79(11):1699-709. doi: 10.2106/00004623-199711000-00012. Erratum in: J Bone Joint Surg Am 1998 Feb;80(2):302. PMID: 9384430.

(6) Fennema EM, Renard AJ, Leusink A, van Blitterswijk CA, de Boer J. The effect of bone marrow aspiration strategy on the yield and quality of human mesenchymal stem cells. Acta Orthop. 2009 Oct;80(5):618-21. doi: 10.3109/17453670903278241. PMID: 19916699; PMCID: PMC2823327.

(7) Magalon J, Bausset O, Serratrice N, Giraudo L, Aboudou H, Veran J, Magalon G, Dignat-Georges F, Sabatier F. Characterization and comparison of 5 platelet-rich plasma preparations in a single-donor model. Arthroscopy. 2014 May;30(5):629-38. doi: 10.1016/j.arthro.2014.02.020. PMID: 24725317.

(8) Berger DR, Centeno CJ, Steinmetz NJ. Platelet lysates from aged donors promote human tenocyte proliferation and migration in a concentration-dependent manner. Bone Joint Res. 2019 Feb 2;8(1):32-40. doi: 10.1302/2046-3758.81.BJR-2018-0164.R1. PMID: 30800297; PMCID: PMC6359887.

If you have questions or comments about this blog post, please email us at [emailprotected]

NOTE: This blog post provides general information to help the reader better understand regenerative medicine, musculoskeletal health, and related subjects. All content provided in this blog, website, or any linked materials, including text, graphics, images, patient profiles, outcomes, and information, are not intended and should not be considered or used as a substitute for medical advice, diagnosis, or treatment. Please always consult with a professional and certified healthcare provider to discuss if a treatment is right for you.

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Bone Marrow Stem Cell Dose Matters in Knee Osteoarthritis

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Predicting the risk of acute kidney injury after hematopoietic stem cell transplantation: development of a new predictive nomogram | Scientific...

Recently, an impressive development in embryology was reported by the Israeli Weizmann Institute of Science. Using only stem cells, without the presence of sperm, eggs, or even a womb, researchers successfully created functioning mouse embryos, complete with beating hearts, blood circulation, brain tissue and rudimentary digestive systems. Carolyn Johnson in The Washington Post described the discovery as a fascinating, potentially fraught realm of science that could one day be used to create replacement organs for humans.

For the more than 100,000 people currently waiting for a life-saving organ donation, that kind of breakthrough would indeed seem like a miracle. However, since scientists are still years away from creating human organs in a lab for the purpose of transplant, the technology raises serious ethical questions, none of which should be taken lightly.

One of these questions is, in fact, an old one. Do the promises of embryonic stem cell research justify it? While some stem cells can be harvested from a variety of non-embryonic sources such as bone marrow, others are harvested from so-called unused embryos that have been donated to science. The lives of these tiny, undeveloped human beings are taken in the process.

For context, the research conducted by the Weizmann Institute uses embryonic stem cells. Though, for the time being, this implies only embryonic stem cells harvested from mice, the move to human research would involve the harvesting of stem cells from human embryos and involve tissue derived from already living human beings.

The Christian stance on when life begins is the same as the science. Human life begins at conception, and every single human life is worthy of protection. If we would not take the life of a born child in our research for a cure for some medical condition, neither the anonymity of an embryo nor the confines of a laboratory justify doing the same thing in the process of embryonic stem cell research.

Science is a process of trial and error, but we should never employ trial and error with the lives of thousands of human beings, in particular human beings who cannot consent to our actions. A rule of thumb is this. If you wouldnt try an experiment on an adult or small child, dont do it to human embryos at any stage.

The breakthrough at the Weizmann Institute, however, takes this old debate a step further. On one hand, lead researcher Dr. Jacob Hanna was quick to clarify that the goal is not to make complete, living organisms of mice or any other species. We are really facing difficulties making organs, he said, and in order to make stem cells become organs, we need to learn how the embryo does that.

Given the history of science, including the last chapter involving breathless promises of what embryonic stem cell research would bring, the grandiose predictions of scientists should be taken with at least a grain of salt. The process of growing organs for mice, for example, involved the creation of entire embryos. Should the technology be perfected in mice, what ethical or legal limits are there to prevent the creation of synthetic human embryos for the purpose of harvesting their organs?

Our first concern should be what these embryos would be created for. The answer is, inevitably, science, devoid of any consideration for human purpose, relationships, worth, or dignity as equal members of the human species. All societies that treat people as a means of scientific advancement, instead of infinitely valuable ends in-and-of themselves, have a track record of perpetrating atrocities.

A second concern is what these embryos would be deprived of. Though not all do, every human should enter the world with the love and commitment of their biological mom and dad. The very design of human development suggests this, and societies have long recognized that those born without these relationships have had something priceless taken from them. Creating children from cloning or stem cells intentionally makes them orphans, ripping them from the vital context of parental relationship. It is a grave injustice.

Bringing children into the world as a product of pure science without the possibility of relationship with their biological parents or relatives is enough an ethical consideration to oppose such research, but we should also consider the implications of recklessly creating humans for future experimentation and of dismantling them to see how their components work.

Science is, in many ways, blind to what should be ethical bright lines. Creating organs for transplant in order to save lives is a worthy goal. But such work should only proceed in an ethical manner, one which does not require the death of other distinct, valuable, human beings. Unfortunately, such ideas have not shaped the society we live in today.

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Creating Organs Cannot Be at the Expense of Human Embryos - BreakPoint.org

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Brave Aubrey Austin, four, donated her own stem cells and saved her baby brother Carey's life on the day he turned one, after he was diagnosed with a rare type of blood cancer aged just eight months

Image: Supplied via Lucy Laing)

A brave little girl saved the life of her baby brother on his first birthday.

Carey Austin was diagnosed with a rare type of blood cancer when he was just eight months old.

His only hope of survival was a stem-cell transplant.

Against all odds, his sister Aubrey, four, was a perfect match.

Surgeons operated on Careys first birthday and six months later he is cancer-free thanks to his big sister.

Image:

Their mum Naomi said: She absolutely adores Carey and when we explained to her about the transplant she wanted to do everything she could to save him.

Shes only four years old, yet she was only thinking of how she could help him. We felt so guilty putting her through an operation too, but it was Careys only chance of survival.

"She was so brave about it. She knew that her blood was going to save him.

During a two-hour procedure at Great Ormond Street Hospital, London, surgeons took out Aubreys stem cells and they were put into Careys body via a drip.

Naomi said: The fact that the transplant took place on Careys birthday was so significant that she was giving him a second chance at life on that special day.

The doctors and nurses said they had never seen anyone have a stem cell transplant on their birthday before.

Aubrey was very groggy and woozy when she came around from the operation, and she had puncture wounds on her back from where the stem cells had been taken out.

But she was still smiling through it all. She was so brave. She never complained about being in pain and she was just pleased to see how her little brother was afterwards.

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When the brother and sister saw each other for the first time after the operation, there was not a dry eye in the room.

Naomi said: It was so sweet when they were reunited.

We took Aubrey to see Carey and she gave him a cuddle. They were thrilled to see each other again.

After a two-day hospital stay for Aubrey and seven weeks for Carey, the family were able to settle back into life back home in Brighton, East Sussex.

Carey is now in remission, with no signs of the cancer cells in his body.

But his parents have been warned that the disease is so aggressive that until March next year there is a 40% chance of it returning. After that, the likelihood falls to just 5%.

Naomi added: Two other children lost their lives on the cancer ward while we were there, so we know how lucky Carey has been.

He and Aubrey have always been close but now their bond is stronger than ever.

"Shes a superstar and he couldnt have wanted anything more from a big sister. Hes doing so well now. He loves playing with his cars and hes just learning to walk too.

Aubrey is with him all the time she just adores him. She knows that she has saved his life and she loves being a big sister to him. They play cars together and hes learning to walk, so she stands with him encouraging him to take his steps.

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Carey fell ill last November but Naomi, a paediatric audiologist, and her husband Simon, a CPS lawyer, both 43, thought it was bronchitis because his sister had recently had the same thing.

A GP agreed but two days later he was rushed to hospital by ambulance with breathing difficulties.

Doctors at Great Ormond Street diagnosed juvenile myelomonocytic leukaemia, or JMML, which cannot be treated with chemotherapy. There are only 1.2 cases per million children in the UK each year.

Naomi said: I was hysterical. I kept trying to tell them that it wasnt cancer, it was bronchilitis. I couldnt accept what was happening.

Because parents are not suitable donors, Aubreys bone marrow was tested, a process that involves drawing a sample out using a needle.

Naomi said: There is only a 25% chance of any sibling being a match, so even with Aubrey we knew that the odds werent in our favour.

"If she hadnt been a match then we would have had to wait until doctors found an anonymous donor, but that may not have happened in time for Carey.

When the results came back to say that she was a perfect match for him, we couldnt believe it. We had been praying that she would save him, so to get the news that she was a match for him was just incredible.

When we heard I couldnt stop crying, it was so emotional. To think that Carey was going to have a chance of survival thanks to his big sister was the answer to our prayers.

The mum added: We did feel guilty about putting her through the procedure, but when we spoke to her about it, all she wanted to do was help. We were so proud of her.

The transplant was made even more special as it took place on March 15, which was Careys first birthday, giving the family a double celebration.

They are keen to raise awareness of the cancer symptoms and the charity Childhood Cancer and Leukaemia Group, which has helped them throughout their ordeal.

Naomi said: Having a child with cancer is one of the worst things that can happen to you. We didnt realise that it was leukaemia so we are thankful that it was spotted in time.

We received amazing support throughout from the hospital and from the CCLG.

We feel so lucky that Carey has come through it and it feels like a miracle to have him with us now.

Geoff Shenton, a childrens cancer specialist at Newcastle Upon Tyne Hospitals NHS Foundation, said: In a very small proportion of cases JMML can disappear on its own, but this is rare.

Most children will need a bone-marrow or stem-cell transplant. There is still a significant chance that the disease can relapse. There may be a possibility of a second transplant if this happens, but despite our best efforts, children still die from JMML.

For more information and support visit cclg.org.uk

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Girl, four, saves baby brother's life by donating her stem cells on his 1st birthday - The Mirror

Fast-track status is granted for frontotemporal dementia, next to the existing designation for traumatic spinal cord injury

GELEEN, Netherlands, Sept. 8, 2022 /PRNewswire/ -- The European Union has grantedstem cell biotech Neuroplastan orphan medicinal product designation for the applicability of its stem cell technology platform to frontotemporal dementia (FTD), following a positive opinion from The European Medicines Agency (EMA). With the existing orphan disease designation (ODD) for traumatic spinal cord injury (TSCI), Neuro-Cells is now approved for a fast-track development pathway with market exclusivity for both a trauma-induced and a chronic degenerative central nervous system disorder. This marks an important milestone in the development roadmap of Neuroplast's Neuro-Cells platform, as a stepping stone to other chronic neurodegenerative diseases such as Alzheimer's, ALS and Parkinson's Disease. The potential width in therapeutic applicability of the Neuroplast technology gives perspective to millions of people suffering from neurodegenerative diseases that currently have no outlook on effective treatment.

One technology addresses underlying mechanisms of multiple acute and chronic neurological disorders

Several conditions of the central nervous system, even when they seem unrelated at first and may have distinctive causes, have similar underlying disease mechanisms in common. These include unprogrammed cell death boosted by inflammation. Neuro-Cells, an autologous, bone-marrow derived Advanced Therapy Medicinal Product, addresses that disease mechanism by moderating inflammation of damaged cells in the central nervous system, to limit further impairment. The treatment objective in acute disorders is to limit impact of sudden injury, where the treatment objective in chronic disorders is to limit progression of the disease.

Neuroplast is already running a fast-track development pathway for traumatic spinal cord injury (TSCI), with a Phase II clinical trial in progress. This designation for frontotemporal dementia illustrates the broader applicability of the same technology for acute as well as chronic neurodegenerative disorders, paving the way to explore further applicability to conditions such as ALS, Alzheimer's disease, traumatic brain injury, subarachnoid stroke and Parkinson's Disease.

Orphan disease designation for FTD awarded based on pre-clinical evidence

Orphan disease designations are restricted to products for rare conditions for which there are no satisfactory methods of treatment authorized. It allows for a faster market authorization pathway and ten-year market exclusivity.

Frontotemporal dementia (FTD) is a degenerative condition in the brain that affect approximately 3.8 people in 10,000 persons in the EU. Typical survival rate lies between three and fourteen years from symptom onset, dependent on the FTD variant at play.

For this approval, the European Union followed the positive opinion from the EMA after the EMA followed positive recommendations from the Committee for Orphan Medicinal Products (COMP). COMP partly based their conclusions on the availability of pre-clinical evidence in mice, that showed decrease in neuroinflammation markers and rescue of cognitive and social behavioral deficits. Examples include reduction of anxiety, depressive-like behavior and abnormal social behavior.

Neuroplast CEO Johannes de Munter states:

"This designation for frontotemporal dementia is an important milestone in expanding the Neuro-Cells development to a wider range of therapeutic areas. Using the same technology platform for traumatic spinal cord injury and frontotemporal dementia, illustrates an unusual range of acute and chronic neurological disorders that could potentially benefit from this."

Neuroplast is open to discuss investor opportunities to effectuate the clinical pathways to a wider scope of neurological conditions.

About Frontotemporal dementia

Frontotemporal dementia (FTD) is a degenerative condition in the brain that is characterized by behavioral and language impairments. Depending on the variant, patients experience changes in personality, emotion, speech or motor functions. Patients may first become indifferent or careless and have difficulty understanding sentences. While the condition progresses, patients may become language impaired, lack initiative and lose executive functions. The typical survival rate lies between three and fourteen years from symptom onset, dependent on the FTD variant at play.

FTD affects approximately 3.8 people in 10,000 persons in the EU, for whom there are no effective treatments available. Patients typically receive antipsychotics to limit behavioral symptoms.

About Neuro-Cells

Neuro-Cells is a transformative treatment under GMP. It contains non-substantially manipulated bone marrow-derived hematopoietic and mesenchymal stem cells, manufactured from a patient's own bone marrow (donor and receiver are the same person). Inflammatory inducing components and pathogens are removed during this process.

About Neuroplast

Neuroplast is a Dutch stem cell technology company focusing on fast-track development programs using autologous cell products for treatment of neurodegenerative diseases, with the aim of giving back perspective to people who suffer from those conditions.

The company was founded in August 2014 by physician Johannes de Munter and neurologist Erik Wolters. Current funders are Lumana Invest, Brightlands Venture Partners, LIOF and the Netherlands Enterprise Agency. Neuroplast is located at Brightlands Chemelot Campus in The Netherlands.

For more information, please visite http://www.neuroplast.com

About Lumana Invest

Investment company Lumana was established by entrepreneurs and unique due to not having a predetermined investment horizon. The Lumana founders showcase strong commitment to their portfolio companies by actively supporting management in strategic decision making.

About Brightlands Venture Partners

Brightlands Venture Partners (BVP) is the fund manager of Chemelot Ventures and is a so-called ecosystem investor. BVP invests in companies benefiting from and contributing to the Brightlands campuses in the south of The Netherlands. Other funds under management are BVP Fund IV, Brightlands Agrifood Fund and Limburg Ventures. The funds of BVP focus on sustainability and health; together the funds have made over 40 investments.

About LIOF

LIOF is the regional development agency for Limburg and supports innovative entrepreneurs with advice, network and financing. Together with entrepreneurs and partners, LIOF is working towards a smarter, more sustainable and healthier Limburg by focusing on the transitions of energy, circularity, health and digitalization.

About The Netherlands Enterprise Agency

The Netherlands Enterprise Agency operates under the auspices of the Dutch Ministry of Economic Affairs and Climate Policy. It facilitates entrepreneurship, improves collaborations, strengthens positions and helps realize national and international ambitions with funding, networking, know-how and compliance with laws and regulations.

Forward looking statements

All statements other than statements of historical facts, including the statements about the clinical and therapeutic potential and future clinical milestones of Neuro-Cells, the indications we intend to pursue and our possible clinical or other business strategies, and the timing of these events, are forward-looking statements. Forward-looking statements can be identified by terms such as "believes", "expects", "plans", "potential", "would" or similar expressions and the negative of those terms. These forward-looking statements are based on our management's current beliefs and assumptions about future events and on information currently available to management. Neuroplast B.V. does not make any representation or warranty, express or implied, as to the improper use of this article, accuracy, completeness or updated status of above-mentioned statements. Therefore, in no case whatsoever will Neuroplast B.V. be legally liable or liable to anyone for any decision made or action taken in conjunction with the information and/or statements in this press release or for any related damages.

In case of any further questions, please contact:

Neuroplast

Johannes de Munter, CEOT: +31 (0)85 076 1000E: [emailprotected]

LifeSpring LifeSciences Communication, Amsterdam

Leon MelensT: +31 6 538 16 427E: [emailprotected]

Logo: https://mma.prnewswire.com/media/1666795/Neuroplast_Logo.jpg

SOURCE Neuroplast

Link:
Neuroplast receives second orphan medicinal product designation for Neuro-Cells, paving the way for application to both chronic and trauma-induced...

Stem Cell Differentiation Target Files

Stem cell differentiation involves the changing of a cell to a more specialized cell type, involving a switch from proliferation to specialization. This involves a succession of alterations in cell morphology, membrane potential, metabolic activity and responsiveness to certain signals. Differentiation leads to the commitment of a cell to developmental lineages and the acquisition of specific functions of committed cells depending upon the tissue in which they will finally reside. Stem cell differentiation is tightly regulated by signaling pathways and modifications in gene expression.

Stem cells can be categorized into groups depending on their ability to differentiate.

Embryonic stem cells (ESCs) are pluripotent cells that differentiate as a result of signaling mechanisms. These are tightly controlled by most growth factors, cytokines and epigenetic processes such as DNA methylation and chromatin remodeling. ESCs divide into two cells: one is a duplicate stem cell (the process of self-renewal) and the other daughter cell is one which will differentiate. The daughter cells divides and after each division it becomes more specialized. When it reaches a mature cell type downstream (for example, becomes a red blood cell) it will no longer divide. The ability of ESCs to differentiate is currently being researched for the treatment of many diseases including Parkinson's disease and cancer.

Adult or 'somatic' stem cells are thought to be undifferentiated. Their primary role is to self-renew and maintain or repair the tissue in which they reside.

View all pluripotent stem cell resources available from Bio-Techne.

Regenerative medicine is the repair or replacement of damaged or diseased tissue to restore normal tissue function. This blog post discusses the development of a new cell therapy product derived from PSCs for regenerative medicine use in Parkinson's disease.

Neurons derived from pluripotent stem cells (PSCs) are a source of considerable therapeutic potential for neurodegenerative diseases. This blog post outlines the development of a small molecule-based protocol for the differentiation of human induced PSCs into functional cortical neurons.

Tocris offers the following scientific literature for Stem Cell Differentiation to showcase our products. We invite you to request* your copy today!

*Please note that Tocris will only send literature to established scientific business / institute addresses.

This product guide provides a background to the use of small molecules in stem cell research and lists over 200 products for use in:

Written by Kirsty E. Clarke, Victoria B. Christie, Andy Whiting and Stefan A. Przyborski, this review provides an overview of the use of small molecules in the control of stem cell growth and differentiation. Key signaling pathways are highlighted, and the regulation of ES cell self-renewal and somatic cell reprogramming is discussed. Compounds available from Tocris are listed.

Stem cells have potential as a source of cells and tissues for research and treatment of disease. This poster summarizes some key protocols demonstrating the use of small molecules across the stem cell workflow, from reprogramming, through self-renewal, storage and differentiation to verification. Advantages of using small molecules are also highlighted.

Written by Rebecca Quelch and Stefan Przyborski from Durham University (UK), this poster describes the isolation of pluripotent stem cells, their maintenance in culture, differentiation, and the generation and potential uses of organoids.

Link:
Stem Cell Differentiation | Stem Cells | Tocris Bioscience

Adult stem cells, also called somatic stem cells, are undifferentiated cells that are found in many different tissues throughout the body of nearly all organisms, including humans. Unlike embryonic stem cells, which can become any cell in the body (called pluripotent), adult stem cells, which have been found in a wide range of tissues including skin, heart, brain, liver, and bone marrow are usually restricted to become any type of cell in the tissue or organ that they reside (called multipotent). These adult stem cells, which exist in the tissue for decades, serve to replace cells that are lost in the tissue as needed, such as the growth of new skin every day in humans.

Scientists discovered adult stem cells in bone marrow more than 50 years ago. These blood-forming stem cells have been used in transplants for patients with leukemia and several other diseases for decades. By the 1990s, researchers confirmed that nerve cells in the brain can also be regenerated from endogenous stem cells. It is thought that adult stem cells in a variety of different tissues could lead to treatments for numerous conditions that range from type 1 diabetes (providing insulin-producing cells) to heart attack (repairing cardiac muscle) to neurological disease (regenerating lost neurons in the brain or spinal cord).

Efforts are underway to stimulate these adult stem cells to regenerate missing cells within damaged tissues. This approach will utilize the existing tissue organization and molecules to stimulate and guide the adult stem cells to correctly regenerate only the necessary cell types. Alternatively, the adult stem cells could be isolated from the tissue and grown outside of the body, in cultures. This would allow the cells to be easily manipulated, although they are often relatively rare and difficult to grow in culture.

Because the isolation of adult stem cells does not result in the destruction of human life, research involving adult stem cells does not raise any of the ethical issues associated with research utilizing human embryonic stem cells. Thus, research involving adult stem cells has the potential for therapies that will heal disease and ease suffering, a major focus of Notre Dames stem cell research. Combined with our efforts with induced pluripotent stem (iPS) cells, the Center for Stem Cells and Regenerative Medicine will advance the Universitys mission to ease suffering and heal disease.

Original post:
Adult Stem Cells // Center for Stem Cells and Regenerative Medicine ...

Stem cells are special human cells that can develop into many different types of cells, from muscle cells to brain cells.

Stem cells also have the ability to repair damaged cells. These cells have strong healing power. They can evolve into any type of cell.

Research on stem cells is going on, and it is believed that stem cell therapies can cure ailments like paralysis and Alzheimers as well. Let us have a detailed look at stem cells, their types and their functions.

Also Read: Gene Therapy

Stem cells are of the following different types:

The fertilized egg begins to divide immediately. All the cells in the young embryo are totipotent cells. These cells form a hollow structure within a few days. Cells in one region group together to form the inner cell mass. This contains pluripotent cells that make up the developing foetus.

The embryonic stem cells can be further classified as:

These stem cells are obtained from developed organs and tissues. They can repair and replace the damaged tissues in the region where they are located. For eg., hematopoietic stem cells are found in the bone marrow. These stem cells are used in bone marrow transplants to treat specific types of cancers.

These cells have been tested and arranged by converting tissue-specific cells into embryonic cells in the lab. These cells are accepted as an important tool to learn about the normal development, onset and progression of the disease and are also helpful in testing various drugs. These stem cells share the same characteristics as embryonic cells do. They also have the potential to give rise to all the different types of cells in the human body.

These cells are mainly formed from the connective tissues surrounding other tissues and organs, known as the stroma. These mesenchymal stem cells are accurately called stromal cells. The first mesenchymal stem cells were found in the bone marrow that is capable of developing bones, fat cells, and cartilage.

There are different mesenchymal stem cells that are used to treat various diseases as they have been developed from different tissues of the human body. The characteristics of mesenchymal stem cells depend on the organ from where they originate.

Following are the important applications of stem cells:

This is the most important application of stem cells. The stem cells can be used to grow a specific type of tissue or organ. This can be helpful in kidney and liver transplants. The doctors have already used the stem cells from beneath the epidermis to develop skin tissue that can repair severe burns or other injuries by tissue grafting.

A team of researchers have developed blood vessels in mice using human stem cells. Within two weeks of implantation, the blood vessels formed their network and were as efficient as the natural vessels.

Stem cells can also treat diseases such as Parkinsons disease and Alzheimers. These can help to replenish the damaged brain cells. Researchers have tried to differentiate embryonic stem cells into these types of cells and make it possible to treat diseases.

The adult hematopoietic stem cells are used to treat cancers, sickle cell anaemia, and other immunodeficiency diseases. These stem cells can be used to produce red blood cells and white blood cells in the body.

Stem Cells originate from different parts of the body. Adult stem cells can be found in specific tissues in the human body. Matured cells are specialized to conduct various functions. Generally, these cells can develop the kind of cells found in tissues where they reside.

Embryonic Stem Cells are derived from 5-day-old blastocysts that develop into embryos and are pluripotent in nature. These cells can develop any type of cell and tissue in the body. These cells have the potential to regenerate all the cells and tissues that have been lost because of any kind of injury or disease.

To know more about stem cells, their types, applications and sources, keep visiting BYJUS website.

Stem-cell therapy is the use of stem cells to cure or prevent a disease or condition. The damaged cells are repaired by the generated stem cells, which can also hasten the healing process in the injured tissue. These cells are essential for the regeneration and transplanting of tissue.

Stem cells have the capacity to self-renew and differentiate into specialized cell types. Totipotent stem cells come from an early embryo and can differentiate into all possible types of stem cells.

The four types of stem cells are the embryonic stem cells, adult stem cells, induced pluripotent stem cells and mesenchymal stem cells

Adult stem cells are undifferentiated cells taken from tissues and developing organs. They can replace and restore damaged tissues. Example hematopoietic stem cells in the bone marrow.

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What are Stem Cells? - Types, Applications and Sources - BYJUS

DUBLIN--(BUSINESS WIRE)--The "Induced Pluripotent Stem Cells Market - Growth, Trends, Covid-19 Impact, and Forecasts (2022 - 2027)" report has been added to ResearchAndMarkets.com's offering.

The Induced Pluripotent Stem Cells Market is projected to register a CAGR of 8.4% during the forecast period (2022 to 2027).

Companies Mentioned

Key Market Trends

The Drug Development Segment is Expected to Hold a Major Market Share in the Induced Pluripotent Stem Cells Market.

By application, the drug development segment holds the major segment in the induced pluripotent stem cell market. Various research studies focusing on drug development studies with induced pluripotent stem cells have been on the rise in recent years.

For instance, an article titled "Drug Development and the Use of Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Disease Modeling and Drug Toxicity Screening" published in the International Journal of Molecular Science in October 2020 discussed the broad use of iPSC derived cardiomyocytes for drug development in terms of adverse drug reactions, mechanisms of cardiotoxicity, and the need for efficient drug screening protocols.

Another article published in the Journal of Cells in December 2021 titled "Human Induced Pluripotent Stem Cell as a Disease Modeling and Drug Development Platform-A Cardiac Perspective" focused on methods to reprogram somatic cells into human induced pluripotent stem cells and the solutions to overcome the immaturity of the human induced pluripotent stem cells derived cardiomyocytes to mimic the structure and physiological properties of adult human cardiomyocytes to accurately model disease and test drug safety. Thus, this increase in the research of induced pluripotent stem cells for drug development and drug modeling is likely to propel the segment's growth over the study period.

Furthermore, as per an article titled "Advancements in Disease Modeling and Drug Discovery Using iPSC-Derived Hepatocyte-like Cells" published in the Multi-Disciplinary Publishing Institute journal of Cells in March 2022, preserved differentiation and physiological function, amenability to genetic manipulation via tools such as CRISPR/Cas9, and availability for high-throughput screening, make induced pluripotent stem cell systems increasingly attractive for both mechanistic studies of disease and the identification of novel therapeutics.

North America is Expected to Hold a Significant Share in the Market and Expected to do Same in the Forecast Period

The rise in the adoption of highly advanced technologies and systems in drug development, toxicity testing, and disease modeling coupled with the growing acceptance of stem cell therapies in the region are some of the major factors driving the market growth in North America.

The United States Food and Drug Administration in March 2022 discussed the development of strategies to improve cell therapy product characterization. The agency focused on the development of improved methods for testing stem cell products to ensure the safety and efficacy of such treatments when used as therapies.

Likewise, in March 2020, the Food and Drug Administration announced that ImStem drug IMS001, which uses AgeX's pluripotent stem cell technology, would be available for the treatment of multiple sclerosis. Similarly, REPROCELL introduced a customized iPSC generation service in December 2020, as well as a new B2C website to promote the "Personal iPS" service. This service prepares and stores an individual's iPSCs for future injury or disease regeneration treatment.

Thus, the increasing necessity for induced pluripotent stem cells coupled with increasing investment in the health care department is known to propel the growth of the market in this region.

Key Topics Covered:

1 INTRODUCTION

2 RESEARCH METHODOLOGY

3 EXECUTIVE SUMMARY

4 MARKET DYNAMICS

4.1 Market Overview

4.2 Market Drivers

4.2.1 Increase in Research and Development Activities in Stem Cells Therapies

4.2.2 Surge in Adoption of Personalized Medicine

4.3 Market Restraints

4.3.1 Lack of Awareness Regarding Stem Cell Therapies

4.3.2 High Cost of Treatment

4.4 Porter's Five Force Analysis

5 MARKET SEGMENTATION

5.1 By Derived Cell Type

5.2 Application

5.3 End User

5.4 Geography

6 COMPETITIVE LANDSCAPE

6.1 Company Profiles

7 MARKET OPPORTUNITIES AND FUTURE TRENDS

For more information about this report visit https://www.researchandmarkets.com/r/ylzwhr

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Global Induced Pluripotent Stem Cells Market (2022 to 2027) - Growth, Trends, Covid-19 Impact and Forecasts - ResearchAndMarkets.com - Business Wire

ThisBone Marrow MarketReport provides details on Recent New Developments, Trade Regulations, Import-Export Analysis, Production Analysis, Value Chain Optimization, Market Share, Impact of Domestic and Localized Market Players, Analyzes opportunities in terms of emerging revenue pockets, changing market regulations, strategic market growth analysis, market size, market category growth, niche and application dominance, product endorsements, product launches, geographic expansions , technological innovations in the market.For more information on the bone marrow market, please contact Data Bridge Market Research for a summary of theanalyst, our team will help you make an informed market decision to achieve market growth.

Bone Marrow Market is expected to experience market growth during the forecast period of 2021 to 2028. Data Bridge Market Research analyzes that the market is growing with a CAGR of 5.22% during the forecast period of 2021 to 2028 and it is projected to reach USD 13,899.60 Million by 2028. The increasing number of bone marrow diseases will help accelerate the growth of the bone marrow market.Bone marrow transplant also called hematopoietic stem cell.It is a soft vascular tissue present inside the long bones.It includes two types of stem cells, namely hematopoietic and mesenchymal stem cells.The bone marrow is primarily responsible for hematopoiesis (blood cell formation), lymphocyte production, and fat storage.

Get Report Sample PDF: https://www.databridgemarketresearch.com/request-a-sample/?dbmr=global-bone-marrow-market

The main factors driving the growth of the bone marrow market during the forecast period are the growth in the incidence of non-Hodgkins and Hodgkins lymphoma, thalassemia, and leukemia, as well as common bone marrow diseases worldwide, developments in technology and improvements.in health infrastructure.In addition, advanced signs of bone marrow transplantation for cardiac and neural disorders, increased funding for logistics services, and rising health care spending per capita are some of the other factors expected to further drive growth. growth of the bone marrow market in the coming years.years.However, the high costs of treatment,

Key Players Covered in the Bone Marrow Market Report are AGendia, Agilent Technologies, Inc., Ambrilia Biopharma Inc., Astellas Pharma Inc., diaDexus, Illumina, Inc., QIAGEN, F Hoffmann-La Roche Ltd, Sanofi, Stryker Corporation, PromoCell GmbH, STEMCELL Technologies Inc., Lonza, ReachBio LLC, AllCells, ATCC, Lifeline Cell Technology, Conversant bio, HemaCare, Mesoblast Ltd., Merck KGaA, Discovery Life Sciences, ReeLabs Pvt. Ltd., Gamida Cell, among others national and global players.Market share data is available separately for Global, North America, Europe, Asia-Pacific (APAC), Middle East and Africa (MEA), and South America.DBMR analysts understand competitive strengths and provide competitive analysis for each competitor separately.

For More Information On Market Analysis, View Research Report Summary At :-https://www.databridgemarketresearch.com/reports/global-bone-marrow-market

Bone MarrowMarket Scope and Market Size

The bone marrow market is segmented based on transplant type, disease indication, and end user.Growth between these segments will help you analyze weak growth segments in industries and provide users with valuable market overview and market insights to help them make strategic decisions to identify leading market applications.

Country-level analysis of thebone marrow market

The bone marrow market is analyzed and information is provided on market size and trends by country, transplant type, disease indication, and end user, as mentioned above.Countries Covered in Bone Marrow Market Report are USA, Canada, and Mexico, North America, Germany, France, UK, Netherlands, Switzerland, Belgium, Russia, Italy, Spain, Turkey, Rest of Europe in Europe, China, Japan, India, South Korea, Singapore, Malaysia, Australia, Thailand, Indonesia, the Philippines, Rest of Asia-Pacific (APAC) in the Asia-Pacific region (APAC), Saudi Arabia, United Arab Emirates , South Africa, Egypt, Israel, Rest of the Middle East and Africa (MEA) under Middle East and Africa (MEA), Brazil,

Europe dominates the bone marrow market due to the proliferation of innovative health centers.Furthermore, the health systems have introduced bone marrow transplantation in their contributions and state-of-the-art public facilities that will further drive the growth of the bone marrow market in the region during the forecast period.North America is expected to witness significant growth in the bone marrow market due to increasing cases of chronic diseases such as blood cancer.In addition, the increase in the geriatric population is one of the factors that is expected to drive the growth of the bone marrow market in the region in the coming years.

Explore Full TOC At:- https://www.databridgemarketresearch.com/toc/?dbmr=global-bone-marrow-market

The country section of the Bone Marrow market report also provides individual market impact factors and regulatory changes in the country market that affect current and future market trends.Data points such as consumption volumes, production sites and volumes, import and export analysis, price trend analysis, raw material cost, Downstream and Upstream value chain analysis are some of the main indicators used to forecast the scenario. of the market for each country.Additionally, the presence and availability of global brands and the challenges they face due to significant or rare competition from local and national brands,

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Bone Marrow market estimated to reach US$13899.60 Million during the forecast period - Digital Journal

In 2011, Made In Space created the first 3D printer for microgravity; what sounded like science fiction suddenly became a reality. Since then, at least 15 experimental 3D printers have been tested aboard Zero-G flights worldwide. Powered by companies, academic institutions, and space agencies, this type of 3D printing research has been successful, from a few printers occasionally tested between 2011 and 2018 to half a dozen in 2022 alone.

Looking back at 2011, we might remember it as a year of transition for the space industry, chiefly because it was the beginning of the end for NASAs Space Shuttle program, which took its final flight in July of that year. With a budget trim to go with it, NASA would soon turn to private industry for many of its space needs. One company, in particular, was keen to leave its mark. Known today as the firm that creates 3D printers for the International Space Station (ISS), Made In Space came out of Singularity University looking to fill a space manufacturing gap.

At its core, Made In Space founders believed that 3D printing and in-space manufacturing would dramatically change the way we look at space exploration, commercialization, and mission design today.

Like Made In Space (now part of Redwire), other companies also decided to test their 3D printing technology in parabolic flights. For example, in 2016, engineering firm and regular NASA contractor Techshot (also acquired by Redwire) partnered with manufacturer nScrypt to create the first microgravity bioprinter and tested it in an aircraft flown by the Zero Gravity Corporation, which operates weightless flights from U.S. airports.

Flying at 30,000 ft (roughly 9,144 meters) over the Gulf of Mexico, the plane simulated weightlessness while the bioprinter created cardiac and vascular structures using human stem cells. Like Made In Space, Techshot and nScrypt later sent the bioprinter to the ISS U.S. National Laboratory, where astronauts are using it for manufacturing human knee cartilage test prints and other human tissue.

The idea of manufacturing in space has long posed several obvious challenges, primarily gravity issues, quality controls, and raw material sourcing. However, once in place, in-situ manufacturing has the potential to relax the dependence on resource resupply from Earth, making survival in space a little bit easier.

For decades, in-space manufacturing has been investigated as a method for producing parts and components in orbit that would otherwise be almost impossible to obtain immediately or at all. In the late 1960s, Soviet cosmonauts conducted the first welding experiments in space as part of their space manufacturing research. In the next decade, the United States began experimenting with space manufacturing in Skylab, the first space station launched by NASA.

But the gateway to space manufacturing lies in the investigations of parabolic flights that can reproduce gravity-free conditions in an aircraft right here on Earth. By alternating upward and downward arcs, they provide the necessary microgravity environment for scientists to conduct research without actually traveling to space. This simulated weightlessness may have started in the 1960s with the first flying space labs aboard U.S. military planes. Still, it has expanded to incorporate several private businesses, like US-based company Zero-G and French-based Novespace.

With more options to recreate the unique weightlessness of space, we have witnessed a series of printers that have been successfully tested in parabolic flights. For example, in late 2016, Luke Carter of the Advanced Materials and Processing Laboratory (AMP Lab) at the University of Birmingham demonstrated metal 3D printing in microgravity aboard three separate parabolic flights. By creating a printing process much like directed energy deposition (DED), and using aluminum wire as feedstock, Carter and his team made a near-net shape part.

Then in 2017, the Canadian Reduced Gravity Experiment Design Challenge (CAN-RGX), supported by the National Research Council and the Canadian Space Agency, chose two teams to test their 3D printing experiments in parabolic flights. Team AVAIL (Analyzing Viscosity and Inertia in Liquids) from the University of Toronto built a system that controls the flow of a viscous liquid (corn syrup, in this case) through 15 different nozzles, and Team iSSELab (Interfacial Science and Surface Engineering Lab), hailing from the University of Alberta, collected data from 3D printing materials in a reduced gravity environment.

The following year, a European parabolic flight aircraft in New Zealand took scientists from the Technology and Engineering Center for Space Utilization of the Chinese Academy of Sciences (CAS) to test the first ceramic DLP 3D printer in microgravity. Following this successful event, NASA chose Associate Professor Gregory Whiting and his research group to test and model how 3D printing functional materials would work in lunar gravity. Whitings research group, the Boulder Experimental Electronics and Manufacturing Lab, geared up for two parabolic flights in 2021.

Around that time, engineering students of the Munich University of Applied Sciences built a 3D printer with an extruder to dispense a liquid photopolymer that took off on the European Space Agency (ESA)s 74th parabolic flight campaign from Paderborn-Lippstadt Airport in Germany.

A few memorable 3D printing experiments in zero gravity in 2022 include Space Foundrys testing of space-based electronic printing, supported by NASAs Flight Opportunities and Small Business Innovation Research (SBIR) programs. In addition, UC Berkeley research teams tested the replicator, a light-based 3D printer, on May 10, printing more than 100 objects. Also, a German consortium tested out its patented 3D printing process and, for the first time, used metallic powders to 3D print in zero gravity.

This is just a taste of what is possible here on Earth, thanks to gravity-free flights. These and other experiments that took place in the last few years can be found below.

Stay up-to-date on all the latest news from the 3D printing industry and recieve information and offers from thrid party vendors.

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3D Printers in Zero-G Flights? There Have Been a Few of Those - 3DPrint.com

Figure 1 |. Surface ectoderm and CNCC co-induction leads to hair-bearing skin generation.

a, b

a, b, Overview of (a) study objectives and (b) skin organoid (SkO) protocol. c, Brightfield images of WA25 aggregates on days 12 and 30 in optimized culture. d, Immunostaining for KRT5+KRT15+ basal and KRT15+ peridermal layers at day-55. e, f, Representative HF-induction images (e) in brightfield of days 6585 WA25 SkOs and (f) max-intensity confocal image (endogenous DSP-GFP) of days 6595 DSP-GFP SkO. Dashed-box: magnified-HF; dashed-line: HF; dashed-circles: developing hair germs; asterisks: dermal papilla. g, h, Violin plots showing (g) frequencies of HF-formation in WA25 (average 87.4%, min=68.8%, max=100%, n=212 organoids), DSP-GFP (average 87.2%, min=66.7%, max=100%, n=212 organoids), and WA01 (71%, n=130 organoids) cultures, and (h) average number of HFs formed in WA25 (average 64 HFs/organoid, min=9, max=285, n=80 organoids) and DSP-GFP (average 48 HFs/organoid, min=7, max=128, n=80 organoids) cultures between days 75147. i-k, Immunostained day-75 WA25 SkO with hair placodes. Antibodies highlight epidermal (KRT5+KRT15+CD49f+) and periderm (KRT15+) layers, dermis (PDGFR+P75+), and DC cells (SOX2+PDGFR+P75+). Dashed-boxes: magnified-regions. l, Wholemount of day-85 WA25 SkO with head-tail structures. KRT5 highlights epidermis and HF outer root sheath. SOX2 marks DC, DP, Merkel cells and melanocytes. Dashed-box: area shown to the right. Abbr: frontonasal prominence (FNP); cranial neural crest cells (CNCCs); dermal papilla (DP); matrix (Mtx); periderm (PD); hair root (HR); dermal condensate (DC). Scale: 500 m (c), 250 m (l; left), 100 m (e; first three panels, f; third-panel, i-k; upper-panels), 50 m (d, f; second-panel, i-k; lower-panels, l; right), 25 m (e; last-panel, f; first/last-panels). See Statistics and Reproducibility for plot and experimental information.

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Hair-bearing human skin generated entirely from pluripotent stem cells

FACTORFIVE Skincare The Power of Stem Cells for Skin icon-star icon-bag icon-search icon-close icon-list icon-plus minus icon-loading arrow-left arrow-right chevron-left chevron-right mail linkedin facebook instagram pinterest tumblr youtube stumbleupon google print heart share icon-visa icon-mastercard icon-american-express icon-discover icon-paypal icon-apple-pay icon-stripe

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FACTORFIVE Skincare The Power of Stem Cells for Skin

Hematopoietic Stem Cells: In living organisms, a specialized system that consist of blood and its progenitors are referred to as the hematopoietic system.

In particular, this system is made up of cells with specialized functions such as the red blood cells (for carrying oxygen to tissues), white blood cells (for immune defense against pathogens, and foreign agents), platelets (for blood clotting), macrophages and lymphocytes (also for immune defense).

However, many of the said blood cells are temporary and need to be replaced with new ones continuously. But fret not because a single cell can solve the problem!

Every day, almost billions of new blood cells are synthesized within the body with each coming from a specific progenitor cell called the hematopoietic stem cell.

How to pronounce Hematopoietic Stem Cells?

What is Hematopoiesis?

The formation of all kinds of blood cells including creation, development, and differentiation of blood cells is commonly known as Hematopoiesis or Haemopoiesis.

All types of blood cells are generated from primitive cells (stem cells) that are pluripotent (they have the potential to develop into all types of blood cells).

Also referred to as hemocytoblasts, hematopoietic cells are the stem cells that give rise to blood cells in hematopoiesis.

Where Does Hematopoiesis Occur?

In a healthy adult, hematopoiesis occurs in the bone marrow and lymphatic tissues, where 1000+ new blood cells (all types) are generated from the hematopoietic stem cells to main the steady-state levels.

Where Are Hematopoietic Stem Cells Found?

They can also be found in the umbilical cord and in the blood from the placenta.

Who Discovered Hematopoietic Stem Cells?

It was long believed that the majority of hematopoiesis occurs during ontogeny (origination and development of organism) and that the mammalian hematopoietic system originated from the yolk sac per se.

Functions of Hematopoietic Cells

As alluded to earlier, blood cells and blood cell components are formed in a process called hematopoiesis.

Coming from the Greek words hemato and poiesis which mean blood and to make respectively, hematopoiesis occurs in the bone marrow and is responsible not only for the synthesis but also the multiplication, and differentiation of blood cells.

Shown below is a diagrammatic illustration of the different blood cell types that hematopoietic cells can give rise to:

Clinical uses of Hematopoietic Stem Cells

The mammalian blood system showcases the equilibrium between the functions of hematopoietic stem cells. Intensive studies have already shown the structures and molecules that control these stem cells, but the exact picture of the underlying molecular mechanisms is still unclear.

Above everything else, it is important to note that such issues are not just of academic interest but can also be relevant in devising future novel methods of diagnosing and treating various diseases associated with cells.

Key References

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Hematopoietic Stem Cells | Hematopoiesis | Properties & Functions

Cells in the body have specific purposes, but stem cells are cells that do not yet have a specific role and can become almost any cell that is required.

Stem cells are undifferentiated cells that can turn into specific cells, as the body needs them.

Scientists and doctors are interested in stem cells as they help to explain how some functions of the body work, and how they sometimes go wrong.

Stem cells also show promise for treating some diseases that currently have no cure.

Stem cells originate from two main sources: adult body tissues and embryos. Scientists are also working on ways to develop stem cells from other cells, using genetic reprogramming techniques.

A persons body contains stem cells throughout their life. The body can use these stem cells whenever it needs them.

Also called tissue-specific or somatic stem cells, adult stem cells exist throughout the body from the time an embryo develops.

The cells are in a non-specific state, but they are more specialized than embryonic stem cells. They remain in this state until the body needs them for a specific purpose, say, as skin or muscle cells.

Day-to-day living means the body is constantly renewing its tissues. In some parts of the body, such as the gut and bone marrow, stem cells regularly divide to produce new body tissues for maintenance and repair.

Stem cells are present inside different types of tissue. Scientists have found stem cells in tissues, including:

However, stem cells can be difficult to find. They can stay non-dividing and non-specific for years until the body summons them to repair or grow new tissue.

Adult stem cells can divide or self-renew indefinitely. This means they can generate various cell types from the originating organ or even regenerate the original organ, entirely.

This division and regeneration are how a skin wound heals, or how an organ such as the liver, for example, can repair itself after damage.

In the past, scientists believed adult stem cells could only differentiate based on their tissue of origin. However, some evidence now suggests that they can differentiate to become other cell types, as well.

From the very earliest stage of pregnancy, after the sperm fertilizes the egg, an embryo forms.

Around 35 days after a sperm fertilizes an egg, the embryo takes the form of a blastocyst or ball of cells.

The blastocyst contains stem cells and will later implant in the womb. Embryonic stem cells come from a blastocyst that is 45 days old.

When scientists take stem cells from embryos, these are usually extra embryos that result from in vitro fertilization (IVF).

In IVF clinics, the doctors fertilize several eggs in a test tube, to ensure that at least one survives. They will then implant a limited number of eggs to start a pregnancy.

When a sperm fertilizes an egg, these cells combine to form a single cell called a zygote.

This single-celled zygote then starts to divide, forming 2, 4, 8, 16 cells, and so on. Now it is an embryo.

Soon, and before the embryo implants in the uterus, this mass of around 150200 cells is the blastocyst. The blastocyst consists of two parts:

The inner cell mass is where embryonic stem cells are found. Scientists call these totipotent cells. The term totipotent refer to the fact that they have total potential to develop into any cell in the body.

With the right stimulation, the cells can become blood cells, skin cells, and all the other cell types that a body needs.

In early pregnancy, the blastocyst stage continues for about 5 days before the embryo implants in the uterus, or womb. At this stage, stem cells begin to differentiate.

Embryonic stem cells can differentiate into more cell types than adult stem cells.

MSCs come from the connective tissue or stroma that surrounds the bodys organs and other tissues.

Scientists have used MSCs to create new body tissues, such as bone, cartilage, and fat cells. They may one day play a role in solving a wide range of health problems.

Scientists create these in a lab, using skin cells and other tissue-specific cells. These cells behave in a similar way to embryonic stem cells, so they could be useful for developing a range of therapies.

However, more research and development is necessary.

To grow stem cells, scientists first extract samples from adult tissue or an embryo. They then place these cells in a controlled culture where they will divide and reproduce but not specialize further.

Stem cells that are dividing and reproducing in a controlled culture are called a stem-cell line.

Researchers manage and share stem-cell lines for different purposes. They can stimulate the stem cells to specialize in a particular way. This process is known as directed differentiation.

Until now, it has been easier to grow large numbers of embryonic stem cells than adult stem cells. However, scientists are making progress with both cell types.

Researchers categorize stem cells, according to their potential to differentiate into other types of cells.

Embryonic stem cells are the most potent, as their job is to become every type of cell in the body.

The full classification includes:

Totipotent: These stem cells can differentiate into all possible cell types. The first few cells that appear as the zygote starts to divide are totipotent.

Pluripotent: These cells can turn into almost any cell. Cells from the early embryo are pluripotent.

Multipotent: These cells can differentiate into a closely related family of cells. Adult hematopoietic stem cells, for example, can become red and white blood cells or platelets.

Oligopotent: These can differentiate into a few different cell types. Adult lymphoid or myeloid stem cells can do this.

Unipotent: These can only produce cells of one kind, which is their own type. However, they are still stem cells because they can renew themselves. Examples include adult muscle stem cells.

Embryonic stem cells are considered pluripotent instead of totipotent because they cannot become part of the extra-embryonic membranes or the placenta.

Stem cells themselves do not serve any single purpose but are important for several reasons.

First, with the right stimulation, many stem cells can take on the role of any type of cell, and they can regenerate damaged tissue, under the right conditions.

This potential could save lives or repair wounds and tissue damage in people after an illness or injury. Scientists see many possible uses for stem cells.

Tissue regeneration is probably the most important use of stem cells.

Until now, a person who needed a new kidney, for example, had to wait for a donor and then undergo a transplant.

There is a shortage of donor organs but, by instructing stem cells to differentiate in a certain way, scientists could use them to grow a specific tissue type or organ.

As an example, doctors have already used stem cells from just beneath the skins surface to make new skin tissue. They can then repair a severe burn or another injury by grafting this tissue onto the damaged skin, and new skin will grow back.

In 2013, a team of researchers from Massachusetts General Hospital reported in PNAS Early Edition that they had created blood vessels in laboratory mice, using human stem cells.

Within 2 weeks of implanting the stem cells, networks of blood-perfused vessels had formed. The quality of these new blood vessels was as good as the nearby natural ones.

The authors hoped that this type of technique could eventually help to treat people with cardiovascular and vascular diseases.

Doctors may one day be able to use replacement cells and tissues to treat brain diseases, such as Parkinsons and Alzheimers.

In Parkinsons, for example, damage to brain cells leads to uncontrolled muscle movements. Scientists could use stem cells to replenish the damaged brain tissue. This could bring back the specialized brain cells that stop the uncontrolled muscle movements.

Researchers have already tried differentiating embryonic stem cells into these types of cells, so treatments are promising.

Scientists hope one day to be able to develop healthy heart cells in a laboratory that they can transplant into people with heart disease.

These new cells could repair heart damage by repopulating the heart with healthy tissue.

Similarly, people with type I diabetes could receive pancreatic cells to replace the insulin-producing cells that their own immune systems have lost or destroyed.

The only current therapy is a pancreatic transplant, and very few pancreases are available for transplant.

Doctors now routinely use adult hematopoietic stem cells to treat diseases, such as leukemia, sickle cell anemia, and other immunodeficiency problems.

Hematopoietic stem cells occur in blood and bone marrow and can produce all blood cell types, including red blood cells that carry oxygen and white blood cells that fight disease.

People can donate stem cells to help a loved one, or possibly for their own use in the future.

Donations can come from the following sources:

Bone marrow: These cells are taken under a general anesthetic, usually from the hip or pelvic bone. Technicians then isolate the stem cells from the bone marrow for storage or donation.

Peripheral stem cells: A person receives several injections that cause their bone marrow to release stem cells into the blood. Next, blood is removed from the body, a machine separates out the stem cells, and doctors return the blood to the body.

Umbilical cord blood: Stem cells can be harvested from the umbilical cord after delivery, with no harm to the baby. Some people donate the cord blood, and others store it.

This harvesting of stem cells can be expensive, but the advantages for future needs include:

Stem cells are useful not only as potential therapies but also for research purposes.

For example, scientists have found that switching a particular gene on or off can cause it to differentiate. Knowing this is helping them to investigate which genes and mutations cause which effects.

Armed with this knowledge, they may be able to discover what causes a wide range of illnesses and conditions, some of which do not yet have a cure.

Abnormal cell division and differentiation are responsible for conditions that include cancer and congenital disabilities that stem from birth. Knowing what causes the cells to divide in the wrong way could lead to a cure.

Stem cells can also help in the development of new drugs. Instead of testing drugs on human volunteers, scientists can assess how a drug affects normal, healthy tissue by testing it on tissue grown from stem cells.

Watch the video to find out more about stem cells.

There has been some controversy about stem cell research. This mainly relates to work on embryonic stem cells.

The argument against using embryonic stem cells is that it destroys a human blastocyst, and the fertilized egg cannot develop into a person.

Nowadays, researchers are looking for ways to create or use stem cells that do not involve embryos.

Stem cell research often involves inserting human cells into animals, such as mice or rats. Some people argue that this could create an organism that is part human.

In some countries, it is illegal to produce embryonic stem cell lines. In the United States, scientists can create or work with embryonic stem cell lines, but it is illegal to use federal funds to research stem cell lines that were created after August 2001.

Some people are already offering stem-cells therapies for a range of purposes, such as anti-aging treatments.

However, most of these uses do not have approval from the U.S. Food and Drug Administration (FDA). Some of them may be illegal, and some can be dangerous.

Anyone who is considering stem-cell treatment should check with the provider or with the FDA that the product has approval, and that it was made in a way that meets with FDA standards for safety and effectiveness.

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Stem cells: Sources, types, and uses - Medical News Today

This months top grants in regenerative medicine, sourced from Dimensions, includes projects on: a novel platform to enhance single cell interrogation of nervous system development, human endothelial cell regulation of ossification and the development of a dynamic double network hydrogel for generating pancreatic organoids from induced pluripotent stem cells.

This project aims to investigate a strategy, which utilizes novel spatial transcriptomics approaches, integrated multiplexed RNA/protein detection and visualization and computational algorithms to identify and map molecular markers of the preganglionic neurons in the ventral spinal cord and progenitor cell populations of the sympathetic ganglia. If successful, the approach could provide a foundation for basic research of peripheral nervous system birth defects and repair using stem cell-based therapies, as well as future studies of neuroblastoma initiation.

Funding amount:US$206,000

Funding period: 8 August 2022 31 July 2024

Funder:Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Research organization:Stowers Institute for Medical Research (MO, USA)

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Over one million patients undergo bone repair procedures in the USA annually, with autologous bone grafting remaining the preferred treatment for bone defects. The development of therapies that exploit the osteogenic potential of bone marrow-derived mesenchymal stem cells (bm-MSCs) has been limited due to limited understanding of the regulatory mechanisms of in vivo bm-MSC osteogenesis. Previous research from the group showed that the osteogenic potential of bm-MSCs is dependent on sustained proximity to endothelial cells. The goal of the present study is to elucidate the cellular and molecular mechanisms by which endothelial cells regulate the osteogenic differentiation of bm-MSCs and develop a foundation of knowledge upon which to build therapeutic strategies for bone regeneration utilizing autologous bm-MSCs.

Funding amount:US$442,000

Funding period: 10 August 2022 31 May 2027

Funder:National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Research organization:Boston Childrens Hospital (MA, USA)

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Human induced pluripotent stem cells provide a valuable source of cells for basic research and translational applications. While there have been advances in lineage-specific differentiation of human induced pluripotent stem cells, there remains limited understanding on the impact of matrix stiffness, viscoelasticity and integrin ligand presentation on the multi-stage development of exocrine pancreatic organoids. This research aims to define the influence of matrix properties on the generation of exocrine pancreatic organoids by developing a viscoelastic dynamic double network hydrogel platform with controllable matrix mechanical properties and biochemical motifs. This will advance the application of chemically defined matrices as xeno-free artificial stem cell niches for organoid growth and tissue regeneration applications.

Funding amount:US$468,000

Funding period: 1 August 2022 31 July 2026

Funder:National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Research organization: Indiana University Purdue University Indianapolis (IA, USA)

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Top 3 grants in regenerative medicine: July 2022 - RegMedNet

A Taiwanese AI algorithm maker knows the value of the mind behind a face. The company says its software can perform virtual fashion try-ons and parse a consumers personality with the same selfie.

Perfect Corp. last week pushed a new AI and augmented reality makeup app and a fashion industry tie-in that could seed the market for high-end algorithmic social aspiration. In August, the company went down-market with a beard try-on product.

None of that is to take away from Perfects July decision to start selling the AI Personality Finder. It is a combination of facial-feature mapping and rudimentary psychological data that allegedly tells people not only how emotionally attractive they are, but also, what products to use to increase their visual likability.

At least in the United States, Perfect typically sells to fashion and makeup companies, but it also partners with some firms for their mutual marketing benefit.

For instance, the software firm has created a try-on app for toothpaste maker Colgate that reportedly will show people how much brighter their teeth would be by using a Colgate product.

A selfie and a little measure of insecurity is all that someone needs.

A day later, Perfect said it was working with Nolcha Shows on New York Fashion Week (September 9 to 14), a top appointment on many social calendars. Nolcha, a fashion events promoter, has added try-on features to some segments of the show via its YouCam Makeup app.

Then there is Perfects Personality Finder, a subscription service sold to vendors for use by adults and children. It purports to be a biometric recognition algorithm based on the idea that certain faces belong to certain kinds of minds.

The app could raise eyebrows the way that emotion recognition algorithms have done.

It scans a selfie for as many as 65 facial attributes. Out the other end come scores for neuroticism, agreeableness, openness, conscientiousness and extroversion.

It is not unlike another of Perfects apps, its Skin Analysis tool.

Although Perfect says it will remove from its servers information pertaining to children younger than 16, the primary model it uses to illustrate its software appears to be younger.

It was just in March that Perfect left its parent, CyberLink, to acquire Provident Acquisition in order to register for an IPO this year. Provident is referred to as a blank-check company, which makes it the investing version of stem cells. It has all it needs to be something and is waiting for a nudge.

AI | augmented reality | biometrics | CyberLink | face biometrics | facial analysis | mobile app | Perfect | selfie biometrics | Taiwan

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Beauty maybe be skin deep, but AI finds revenue on the faces surface - Biometric Update

September is observed as Blood Cancer Awareness month all over the world. During this month, activists and stakeholders work to raise awareness about the disease and the efforts being taken to fight blood cancers including leukemia, lymphoma, myeloma and Hodgkins disease.

The term blood cancer is a general description of various hematopoietic cancers. Our blood flows through blood vessels to supply all tissues in the body with nutrients. In the approximately 5 litres of blood circulating in our body there are billions of blood cells that carry out various vital functions. All blood cells originate from hematopoietic stem cells.

Haematopoietic stem cells are known as mother cells and do not yet have a specific function. They are able to renew and differentiate into cells with a specific function, thus replacing cells that die. In bone marrow, blood stem cells divide and develop into progenitor cells. Through further division, the progenitor cells mature and transform into different types of blood cells and then enter the bloodstream, says Dr Nitin Agarwal, HOD, Donor Request Management, DKMS BMST Foundation India.

Blood cancer is an abnormal proliferation (abnormal growth) of cells in the bone marrow especially white blood cells (WBCs). Cancer cells flood the bloodstream and drive out healthy cells. As a result, the blood can no longer perform its basic tasks, such as transporting oxygen and protecting the body from infection.

LeukemiaThis cancer is found in the bone marrow and the bloodstream. It is caused by abnormal rapid production of WBCs and high number of abnormal WBCs which cannot fight against infection, and they impair the bone marrows ability to produce red blood cells and platelets, says Dr Jimmy Mirani, Consultant Onco Surgeon, Wockhardt Hospital, Mumbai Central.

LymphomaA type of blood cancer which affects the lymphatic system, which removes the risk excess fluids from body and generates immune cells. Lymphocytes are blood cells which are used to fight against infections. These abnormal lymphocytes become lymphoma cells which multiply and get collected in the tissues, adds Dr Mirani.

There are two types of lymphoma, namely, Hodgkins lymphoma and non-Hodgkins lymphoma.

Non-Hodgkins lymphoma:It mainly impacts the B-cell or T-cell. This type of lymphoma occurs more commonly than Hodgkins lymphoma. Can vary clinically and diagnostically into slow-growing ones to very aggressive types, notes Dr. Amrita Chakrabarti, Consultant, Haemato-Oncology & Bone Marrow Transplant, Max Hospital, Shalimar Bagh.

Hodgkins lymphoma This type of lymphoma affects the B cells. Broadly divided into classical Hodgkins and nodular lymphocyte predominant types. Occurs in the adolescence or elderly age group.

MyelomaIt is the cancer of plasma cells; WBCs which produce disease and infection fighting anti-bodies. Myeloma cells prevent the functions and productions of these antibodies leaving a week immune system.

Multiple myelomaThis starts in the bone marrow when plasma cells begin to grow uncontrollably. As the cells grow, they compromise the immune system and impair the production and function of white and red blood cells causing bone disease, organ damage and anemia among other conditions, adds Dr Agarwal.

In most cases of blood cancer, the patient feels tired and weak. This happens because the number of red blood cells in the blood starts decreasing due to which there is a lack of blood in the person. Someof the commonsymptoms of blood cancers are fever, severe fatigue, bleeding from gums or skin, back ache, or bone pains, says Dr Pravas Mishra, Head Haematology/ Medical Oncology and BMT, Amrita Hospital, Faridabad.

Patients with myeloma might first present to an orthopaedical with a fracture originating from trivial trauma or to a nephrologist with a kidney dysfunction.Pain in bones and joints can be a symptom of not only arthritis but also blood cancer. Blood cancer is a disease in the bone marrow that is found in large amounts around the bones and joints.

Patientsmight present with nodes in the neck or axilla or groin or swelling in any part of the body. However most often a patientwith blood cancermight present with just a low haemoglobin. It is strongly advised not to ignore any anaemia, warns Dr Mishra.

A person suffering from blood cancer is prone to repeated infections. When leukemia cells develop in the body, then complaints of infection can be seen in the patients mouth, throat, skin, lungs, etc.

People who have cancer tend to have an abnormally low weight. If the body weight is reduced without any obvious cause, then it can be seen as the primary symptom of cancer.

The abnormal formation of leukemia cells in the body prevents the bone marrow from forming healthy blood cells such as platelets. Due to its deficiency, more bleeding problems can be seen from the nose of the patient, during menstruation and gums.

Blood cancer is diagnosed with the help of a wide range of diagnostic methods along clinical evaluation, such as blood tests, bone marrow tests, cytogenetic/karyotyping and molecular analysis, flow cytometry.

Myth: Blood cancer cannot be treated?

Fact: Once a patient is diagnosed with blood cancer, the first concern that comes to ones mind Is blood cancer curable?

Blood cancer is one type of cancer that has a high curability rate especially due to the advancement in the medical field, availability of newer, improved chemotherapy regimens, targeted therapy, and improved infection control measures. Timely diagnosis, especially early diagnosis, increases the chances of cure from blood cancer.Some of the other factors that impact the cure of blood cancer include the age of the patient, physical condition, presence of other comorbidities, stage of the disease, subtype of cancer, molecular factors, whether low grade/high grade, acute or chronic, the body parts that are affected and whether the disease is new onset or has come back after a previous cure.

You must understand that the cure or recovery from cancer is unpredictable, adds Dr. Chakrabarti.

There are cases when the patient has recovered even in the later stages of blood cancer. On the other hand, there are recorded cases where the patient couldnt recover even in the initial stages of blood cancer. So, its important to have realistic expectations and focus on following a healthy lifestyle with the advised treatment and measures. Early diagnosis and treatment play an important role in attaining cure.

Myth: All blood cancer patients need a bone marrow transplant

Fact: No, majority of patients suffering from blood cancers are treated without bone marrow transplant. A combination of chemotherapy, targeted therapy and immunotherapy is the best line of treatment.

Myth: Blood cancer occurs only in children?

Fact: No, blood cancers can occur in all age groups. All have a higher incidence in young children whereas Myeloid Leukaemia (MLL) is more frequently seen in senior citizens.

India is reeling under pressure of many misconceptions that exist amongst people about blood stem cell donation, its process and even its after-effects.

Myth: Once you donate blood stem cells, you will lose them forever.

Fact: Only a fraction of total stem cells is extracted during the process. Also, all the cells are naturally replenished within a few weeks

Myth: Donating stem cells is a really invasive and painful process

Fact: Blood stem cells are collected through peripheral blood stem cell collection (PBSC) which is completely safe and a non-surgical procedure. The process is similar to blood platelet donation that takes approximately three to four hours to complete and the donor can leave the collection center the same day.

Myth: Blood donation and a blood stem cell donation are same

Fact: Unlike blood collection for transfusion, blood stem cells are collected only when there is a match between the donor and patients human leukocyte antigen (HLA) combination (tissue type). So, you could be potentially the only match and life saver for a person with blood cancer in need of a transplant, adds Dr Nitin Agarwal. Blood stem cell donors donate only blood stem cells and the process is similar to a platelet donation.

Myth: Pregnant women cant register

Fact: This is untrue, a woman can register even during her pregnancy.

Myth: Stem cell donation leaves prolonged side-effects

Fact: No, there are no major side effects post blood stem cell donation. A person may only experience minor flu like symptoms because of the GCSF injections given to him/her before the donation, to mobilize blood stem cells in your blood stream.

Myth: Piercing and/or tattoo is a restricting factor

Fact: Piercing or a tattoo doesnt stop you from registering yourself to be a potential donor.

Myth: My blood stem cells can be stored

Fact: Your blood stem cells will not be stored. They last for around 72 hours and are delivered for the recipient straight to the hospital by a special courier. If the recipients body accepts them, the stem cells will start making healthy blood cells.

Myth: Joining a blood stem cell registry is no use. Most patients can find a stem cell donor within their own families

Fact: Per statistics, only 30% of blood disorder patients in need of a stem cell transplant are able to find a sibling match. About 70% of patients need an unrelated donor.

A registry like DKMS BMST Foundation India is a data bank of potential blood stem cell donors that houses details on thousands of committed blood stem cell donors. Any patient can benefit from this registry provided an HLA match.

Some of the blood cancer treatments include the following

Chemotherapy

This is the most important aspect of blood cancer treatment and involves using certain chemicals to kill the cancer-causing cells in the patients body. The prescribed drugs are given in a particular timeframe for the best possible improvement in the patients health. In some patients, a stem cell transplant is provided along with high dose chemotherapy.

Radiation therapyRadiation therapy helps to destroy cancer cells with the help of specific high-energy beams to kill cancer cells in precise areas of the body. This treatment is much beneficial for patients with lymphoma

Bone marrow transplantIn this procedure, healthy stem cells are utilized to replace the cells affected by cancer. This helps the patients recover in the best possible manner. Can be autologous (where stem cells are taken from the patients own body) or allogenic (when a healthy donor gives stem cells to the patient.)

Targeted Therapy

Usually in the form of oral medications or pills. They are given alongside chemotherapy/ or radiotherapy and affect specific cancer cells and help in destroying them.

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September is Blood Cancer Awareness Month: All You Need to Know - News18

Memory seems simple enough. For most people, its the ability to create and retrieve memories or information. In reality, memory is a mysterious rabbit hole. Its still not fully understood, especially in the natural world where strange forms of memory exist in chemical compounds and even rocks. There are anthills where memories outlast the ants, and some plants remember being dropped. These facts, and others, might just prove that memory is more amazing than we ever thought possible.

Related: 10 Weird Things You Did Not Know About Memory

A few years ago, evolutionary ecologist Monica Gagliano set out to prove that plants are more intelligent than we give them credit for. More specifically, she wanted to show that plants can learn and remember even though they have no brains. For her experiment, she chose the species Mimosa pudica, a plant that responds to touch by rapidly closing its leaves.

Gagliano created a custom shelf for the plants, one that would suddenly drop a few feet. At first, the plants reacted in a defensive manner and curled their leaves. But after a few drops, the plants seemed to realize there was no danger and stopped clamming up.

Gagliano halted the experiment for a month to give the plants enough time to forget, but they didnt. When the shelf dropped again, none of the Mimosas closed upa tantalizing sign that the plants remembered the falling shelf and that it was also a safe experience.[1]

For a long time, biologists believed that giant tortoises were about as intelligent as a cabbage. However, this misconception lost traction when two zoos tested Galapagos and Aldabra tortoises and discovered that the large reptiles were quick learners. After dangling food as a reward, the tortoises were given two tests. In one instance, they simply had to bite a ball on a stick to get a snack. In the second test, they were shown two balls, but in order to be fed, they had to bite the right color ball.

One zoo tested the animals one by one and got good results. The second zoo tested them in groups, and incredibly, these tortoises seemed to grasp what was expected of them by watching what their fellow tortoises did. Not only did this prove that these animals are capable of individual and social learning, but some of them even remembered to bite the correct color ball when they were tested again nine years later.[2]

In 2018, scientists tested a substance called vanadium dioxide (VO2). The compound was hiding a mystery. For some reason, VO2s resting state made it an insulator, but when heated to above 154.4F (68C), it turned into a conductor. The study revealed why; VO2 has atoms that are capable of rearranging themselves. When heated, they adopt a pattern that turns the compound into a conductor. As it cools, the atoms relax back into their original positions and turn the material back into an insulator.

Remarkably, when researchers heated the VO2 a second time, the atoms behaved as if they remembered the experience of shifting between the two states. Although the discovery is groundbreakingits the first material to behave in this wayVO2 wont win any memory contests. It only seems to remember the shift for three hours after the fact.[3]

Our skin contains plenty of stem cells. When there is a cut or infection, stem cells rush to repair the skin, and they remember the experience. This inflammation memory is mostly a good thing. It helps stem cells respond faster the next time they sense a wound, which speeds up healing times.

However, when researchers looked more closely at the process, they realized that it could be the smoking gun pointing to a new suspect behind inflammatory skin disorders such as psoriasis. In the past, the blame was squarely placed on immune cells. But new studies revealed that the same memory that makes stem cells more effective can also go haywire. As the theory goes, when this happens, the cells hijack the skins inflammatory process, which might either cause psoriasis or make the condition worse.[4]

When a caterpillar turns into a moth or butterfly, the metamorphosis is one of the most drastic in nature. Can memory survive a process that rearranges a creatures entire body? To find out, researchers knew they had to give the caterpillars an enduring memorylike a bad smell. Even better, a pong accompanied by pain. Soon enough, the caterpillars were exposed to light electric shocks accompanied by the smell of nail polish remover.

The caterpillars soon learned to avoid the odor, and remarkably, after they blossomed into moths, the memory and skittishness around the nail polish remover remained. This proved that moths, and probably butterflies too, can remember things from their caterpillar days even though their brains and nervous systems have undergone extensive reshuffling.[5]

Rocks have a curious ability. They can align their magnetic bits with the Earths magnetic field. The manner in which these bits arrange themselves and settle down can act like a snapshot of the planets field. Aptly called magnetic memory, the effect on a rock is permanent, and it gives geologists a way to see how strong or weak the Earths field was a thousand or even millions of years ago.

But when researchers looked at the Devonian period (420 to 360 million years ago), they discovered that rocks from this era have no magnetic memory. What caused this worldwide blank? Thus far, the entire thing remains a compelling mystery. But a leading theory suggests that Earths magnetic field was so disastrously weak that it had no influence on magnetic particles inside stones.[6]

The human brain and ant colonies have a few things in common. They operate without central control, and both also use chemical signals to alter the behavior of important interacting parts. The latter include neurons in brains and ants in colonies.

Researchers were curious to know if ant colonies could also remember things like a brain. To clarify, not the ants. The colony. In other words, could ants behave in a way that suggests they remain affected by something originally experienced by their long-gone predecessors? Incredibly, it would appear so.

Experiments showed that when some nests suffered a disturbance, the ants changed their behavior. Thats not really unusual. But in some cases, subsequent generations of ants also adopted the new behavior even though they were unaware of the disturbance. In this manner, it would appear that a colony can remember a threat when individual ants no longer do.[7]

A few years ago, scientists fitted mosquitoes with tiny helmets. No, really. The hats monitored the brain activity of each mosquito to discover more about its memory processes. The study, which placed the insects in a flight simulator and exposed them to different human chemicals, revealed something interesting.

First, it proved that an old wives tale was true. Mosquitoes find the blood of some people sweeter, and they remember these hosts, often snacking on the same person more than once. The helmets also revealed that mosquitoes are far from dumb because they also remember people who swat at them. Once they recognize the smell of a defensive food source, some mosquitoes abandon the person even though their blood is of the sweet variety.[8]

Gamma-aminobutyric acid (GABA) is a molecule that can be found in humans and animals. It acts as a messenger of the nervous system, which includes the brain. Plants lack brains, and yet, they also have GABA. It helps them with memory-like processes during times of drought, something that surprised the researchers who stumbled upon the fact in 2021.

With plants, GABA works in a simple yet ingenious way to help them limit their water loss in times of drought. During the day, the molecules accumulate within the plants tissues. The drier the weather, the more GABA molecules cram into the fibers. The total amount of GABA then acts like a memory the next day. For example, a dense cluster will remind the plant that yesterday was dry. As a result, the plant protects its internal moisture reserve by not opening its leaf pores too widely.[9]

Slime molds dont have brains or a nervous system. Despite these missing pieces, their minds are surprisingly sophisticated. Experts already knew that slime molds can learn things about their environment and even share these memories with their fellow slime balls. The question was how.

This riddle was cracked in 2019 when researchers noticed that members of one species, Physarum polycephalum, often fused their venous systems with each other. This suggested that individuals can teach other blobs by sharing information through their fused veins. But how do they learn something in the first place?

A test, which used salt as an obstacle to food, threw some light on the learning process. In essence, the blobs get their information by absorbing the item theyre investigating. In this case, they hoovered a little salt, realized it wasnt dangerous, and vein-mailed their fellow blobs the good news.[10]

Jana earns her beans as a freelance writer and author. She wrote one book on a dare and hundreds of articles. Jana loves hunting down bizarre facts of science, nature and the human mind.

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10 Facts That Prove Memory Is Not What You Think - Listverse

BOTHELL, Wash. & TOKYO & RAHWAY, N.J.--(BUSINESS WIRE)-- Seagen, Inc.(Nasdaq:SGEN), Astellas Pharma US, Inc.(TSE:4503, President and CEO: Kenji Yasukawa, Ph.D., Astellas) and Merck & Co. (NYSE: MRK), known as MSD outside of the United States and Canada, today announced results from the phase 1b/2 EV-103 clinical trial (also known as KEYNOTE-869) Cohort K investigating PADCEV (enfortumab vedotin-ejfv) in combination with Mercks anti-PD-1 therapy KEYTRUDA (pembrolizumab) and PADCEV alone as first-line treatment in patients with unresectable locally advanced or metastatic urothelial cancer (la/mUC) who are ineligible to receive cisplatin-based chemotherapy. The findings were presented today at the European Society for Medical Oncology (ESMO) Congress as part of a late-breaking abstract presentation (Abstract #LBA73).

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20220912005300/en/

In patients treated with enfortumab vedotin and pembrolizumab (n=76), results demonstrated a 64.5% confirmed objective response rate (ORR) (95% CI: 52.7 to 75.1) per RECIST v1.1 by blinded independent central review (BICR), the primary endpoint of Cohort K, with 10.5% of patients experiencing a complete response and 53.9% of patients experiencing a partial response. The median duration of response (DOR) per BICR was not reached (95% CI: 10.25 months to NR). All-grade treatment-related adverse events (TRAEs) of special interest for enfortumab vedotin in combination with pembrolizumab were skin reactions (67.1%), peripheral neuropathy (60.5%), ocular disorders (dry eye, blurred vision, and corneal disorders) (26.3%), hyperglycemia (14.5%), and infusion-related reactions (3.9%). Pembrolizumab adverse events of special interest were consistent with previously observed safety data from monotherapy with the exception of severe skin reactions. Overall, the results were generally consistent with previously reported efficacy and safety results of the EV-103/KEYNOTE-869 dose-escalation cohort and expansion Cohort A.1

Please see Important Safety Information at the end of this press release for both drugs, including BOXED WARNING for enfortumab vedotin and immune-mediated adverse reactions for pembrolizumab.

Cohort K also included a monotherapy arm in which patients were treated with enfortumab vedotin alone (n=73), though this study was not designed to support a formal comparison between the two arms. Results showed a 45.2% confirmed ORR (95% CI: 33.5 to 57.3) per RECIST v1.1 by BICR, with 4.1% of patients experiencing a complete response and 41.1% of patients experiencing a partial response. The median DOR was 13.2 months (95% CI: 6.14 to 15.97) per RECIST v1.1 by BICR. All-grade TRAEs of special interest for enfortumab vedotin were peripheral neuropathy (54.8%), skin reactions (45.2%), ocular disorders (dry eye, blurred vision, and corneal disorders) (28.8%), hyperglycemia (11.0%), and infusion-related reactions (5.5%).

Additional secondary endpoints in the EV-103 Cohort K trial included progression-free survival (PFS) and overall survival (OS). Among patients treated with enfortumab vedotin and pembrolizumab, median PFS was not reached (95% CI: 8.31 months to NR). Median OS was 22.3 months (95% CI: 19.09 to NR). Among patients treated with enfortumab vedotin, median PFS was 8.0 months (95% CI: 6.05 to 10.35) and median OS was 21.7 months (95% CI: 15.21 to NR).

TRAEs of any grade that occurred in more than 20% of patients treated with enfortumab vedotin alone or in combination with pembrolizumab were fatigue, peripheral sensory neuropathy, alopecia, rash maculo-papular, pruritus, dysgeusia, weight decreased, diarrhea, decreased appetite, nausea, and dry eye.

Results from EV-103/KEYNOTE-869 Cohort K support the ongoing investigation of enfortumab vedotin and pembrolizumab in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who are in need of treatment options, and this combination may be an important therapeutic option for these patients, said Jonathan E. Rosenberg, M.D., Chief, Genitourinary Medical Oncology Service, Division of Solid Tumor Oncology, and Enno W. Ercklentz Chair, Memorial Sloan Kettering Cancer Center and EV-103/KEYNOTE-869 Cohort K primary investigator. Dr. Rosenberg has consulting relationships with Seagen, Astellas and Merck.

Nearly sixty-five percent of patients who were treated with enfortumab vedotin and pembrolizumab responded to the combination, with almost eleven percent showing no detectable cancer following treatment. These study results represent an encouraging finding for people with advanced urothelial cancer who are not eligible for cisplatin treatment, said Marjorie Green, Senior Vice President and Head of Late-Stage Development, Seagen.

We're encouraged by these positive findings from the combination of enfortumab vedotin and pembrolizumab in people with advanced urothelial cancer who historically have had limited treatment options in the first-line setting, and we intend to discuss these results with regulatory authorities, said Ahsan Arozullah, M.D., M.P.H., Senior Vice President and Head of Development Therapeutic Areas, Astellas.

Were pleased that this combination provided a meaningful benefit to this group of advanced bladder cancer patients in this study, and we will continue to investigate enfortumab vedotin plus pembrolizumab through our collaboration, said Dr. Eliav Barr, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, Merck Research Laboratories.

In February 2020, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation for enfortumab vedotin in combination with pembrolizumab for patients with unresectable la/mUC who are ineligible to receive cisplatin-based chemotherapy in the first-line setting. The designation is based on results from the dose-escalation cohort and expansion Cohort A of the phase 1b/2 trial, EV-103/KEYNOTE-869 (NCT03288545), evaluating patients with la/mUC who are ineligible to receive cisplatin-based chemotherapy treated in the first-line setting with enfortumab vedotin in combination with pembrolizumab.

Seagen, Astellas and Merck are further investigating enfortumab vedotin plus pembrolizumab in Phase 3 studies, including EV-302/KEYNOTE-A39 (NCT04223856), which is intended to confirm these results for the investigational treatment combination in previously untreated la/mUC and in muscle-invasive bladder cancer in EV-304/KEYNOTE-B15 (NCT04700124) and EV-303/KEYNOTE-905 (NCT03924895).

About Bladder and Urothelial Cancer

It is estimated that approximately 83,730 people in the U.S. were diagnosed with bladder cancer in 2021.2 Urothelial cancer accounts for 90% of all bladder cancers and can also be found in the renal pelvis, ureter and urethra.3 Globally, approximately 573,000 new cases of bladder cancer and 212,000 deaths are reported annually.4

About the EV-103/KEYNOTE-869 Trial (Cohort K)

The EV-103 trial (NCT03288545) is an ongoing, multi-cohort, open-label, multicenter phase 1b/2 trial of enfortumab vedotin alone or in combination with pembrolizumab and/or chemotherapy in first- or second-line settings in patients with locally advanced or metastatic urothelial cancer (la/mUC) and in patients with muscle-invasive bladder cancer.

Cohort K of the EV-103/KEYNOTE-869 trial is a randomized 1:1 cohort investigating enfortumab vedotin alone (n=73) or in combination with pembrolizumab (n=76) in adult patients with unresectable la/mUC who are ineligible for cisplatin-based chemotherapy and have received no prior treatment for la/mUC. The enfortumab vedotin monotherapy study arm is intended to characterize the activity of enfortumab vedotin alone in this patient population. The key outcome measure of EV-103/KEYNOTE-869 Cohort K is objective response rate (ORR) per blinded independent central review (BICR) using RECIST 1.1. Secondary endpoints include ORR per investigator assessment; duration of response (DOR), disease control rate (DCR) and progression-free survival (PFS) per BICR and investigator assessment; overall survival (OS); and assessment of safety.

About PADCEV

PADCEV (enfortumab vedotin-ejfv) is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.5 Nonclinical data suggest the anticancer activity of PADCEV is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).6

PADCEV (enfortumab vedotin-ejfv) U.S. Indication & Important Safety Information

BOXED WARNING: SERIOUS SKIN REACTIONS

Indication

PADCEV is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC) who:

Important Safety Information

Warnings and Precautions

Skin reactions Severe cutaneous adverse reactions, including fatal cases of SJS or TEN, occurred in patients treated with PADCEV. SJS and TEN occurred predominantly during the first cycle of treatment but may occur later. Skin reactions occurred in 55% of the 680 patients treated with PADCEV in clinical trials. Twenty-three percent (23%) of patients had maculo-papular rash and 33% had pruritus. Grade 3-4 skin reactions occurred in 13% of patients, including maculo-papular rash, rash erythematous, rash or drug eruption, symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), dermatitis bullous, dermatitis exfoliative, and palmar-plantar erythrodysesthesia. In clinical trials, the median time to onset of severe skin reactions was 0.6 months (range: 0.1 to 6.4). Among patients experiencing a skin reaction leading to dose interruption who then restarted PADCEV (n=59), 24% of patients restarting at the same dose and 16% of patients restarting at a reduced dose experienced recurrent severe skin reactions. Skin reactions led to discontinuation of PADCEV in 2.6% of patients. Monitor patients closely throughout treatment for skin reactions. Consider topical corticosteroids and antihistamines, as clinically indicated. Withhold PADCEV and refer for specialized care for suspected SJS or TEN or for severe (Grade 3) skin reactions. Permanently discontinue PADCEV in patients with confirmed SJS or TEN, or for Grade 4 or recurrent Grade 3 skin reactions.

Hyperglycemia and diabetic ketoacidosis (DKA), including fatal events, occurred in patients with and without pre-existing diabetes mellitus, treated with PADCEV. Patients with baseline hemoglobin A1C 8% were excluded from clinical trials. In clinical trials, 14% of the 680 patients treated with PADCEV developed hyperglycemia; 7% of patients developed Grade 3-4 hyperglycemia. The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C. Five percent (5%) of patients required initiation of insulin therapy for treatment of hyperglycemia. The median time to onset of hyperglycemia was 0.6 months (range: 0.1 to 20.3). Hyperglycemia led to discontinuation of PADCEV in 0.6% of patients. Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. If blood glucose is elevated (>250 mg/dL), withhold PADCEV.

Pneumonitis Severe, life-threatening or fatal pneumonitis occurred in patients treated with PADCEV. In clinical trials, 3.1% of the 680 patients treated with PADCEV had pneumonitis of any grade and 0.7% had Grade 3-4. In clinical trials, the median time to onset of pneumonitis was 2.9 months (range: 0.6 to 6). Monitor patients for signs and symptoms indicative of pneumonitis, such as hypoxia, cough, dyspnea or interstitial infiltrates on radiologic exams. Evaluate and exclude infectious, neoplastic and other causes for such signs and symptoms through appropriate investigations. Withhold PADCEV for patients who develop persistent or recurrent Grade 2 pneumonitis and consider dose reduction. Permanently discontinue PADCEV in all patients with Grade 3 or 4 pneumonitis.

Peripheral neuropathy (PN) occurred in 52% of the 680 patients treated with PADCEV in clinical trials, including 39% with sensory neuropathy, 7% with muscular weakness and 6% with motor neuropathy; 4% experienced Grade 3-4 reactions. PN occurred in patients treated with PADCEV with or without pre-existing PN. The median time to onset of Grade 2 PN was 4.6 months (range: 0.1 to 15.8 months). Neuropathy led to treatment discontinuation in 5% of patients. Monitor patients for symptoms of new or worsening peripheral neuropathy and consider dose interruption or dose reduction of PADCEV when PN occurs. Permanently discontinue PADCEV in patients who develop Grade 3 PN.

Ocular disorders were reported in 40% of the 384 patients treated with PADCEV in clinical trials in which ophthalmologic exams were scheduled. The majority of these events involved the cornea and included events associated with dry eye such as keratitis, blurred vision, increased lacrimation, conjunctivitis, limbal stem cell deficiency, and keratopathy. Dry eye symptoms occurred in 34% of patients, and blurred vision occurred in 13% of patients, during treatment with PADCEV. The median time to onset to symptomatic ocular disorder was 1.6 months (range: 0 to 19.1 months). Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders.

Infusion site extravasation Skin and soft tissue reactions secondary to extravasation have been observed after administration of PADCEV. Of the 680 patients, 1.6% of patients experienced skin and soft tissue reactions, including 0.3% who experienced Grade 3-4 reactions. Reactions may be delayed. Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. Two patients (0.3%) developed extravasation reactions with secondary cellulitis, bullae, or exfoliation. Ensure adequate venous access prior to starting PADCEV and monitor for possible extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions.

Embryo-fetal toxicity PADCEV can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during PADCEV treatment and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 4 months after the last dose.

Adverse Reactions

Most Common Adverse Reactions, Including Laboratory Abnormalities (20%)

Rash, aspartate aminotransferase (AST) increased, glucose increased, creatinine increased, fatigue, PN, lymphocytes decreased, alopecia, decreased appetite, hemoglobin decreased, diarrhea, sodium decreased, nausea, pruritus, phosphate decreased, dysgeusia, alanine aminotransferase (ALT) increased, anemia, albumin decreased, neutrophils decreased, urate increased, lipase increased, platelets decreased, weight decreased and dry skin.

EV-301 Study: 296 patients previously treated with a PD-1/L1 inhibitor and platinum-based chemotherapy.

Serious adverse reactions occurred in 47% of patients treated with PADCEV; the most common (2%) were urinary tract infection, acute kidney injury (7% each) and pneumonia (5%). Fatal adverse reactions occurred in 3% of patients, including multiorgan dysfunction (1.0%), hepatic dysfunction, septic shock, hyperglycemia, pneumonitis and pelvic abscess (0.3% each). Adverse reactions leading to discontinuation occurred in 17% of patients; the most common (2%) were PN (5%) and rash (4%). Adverse reactions leading to dose interruption occurred in 61% of patients; the most common (4%) were PN (23%), rash (11%) and fatigue (9%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common (2%) were PN (10%), rash (8%), decreased appetite and fatigue (3% each). Clinically relevant adverse reactions (<15%) include vomiting (14%), AST increased (12%), hyperglycemia (10%), ALT increased (9%), pneumonitis (3%) and infusion site extravasation (0.7%).

EV-201, Cohort 2 Study: 89 patients previously treated with a PD-1/L1 inhibitor and not eligible for platinum-based chemotherapy.

Serious adverse reactions occurred in 39% of patients treated with PADCEV; the most common (3%) were pneumonia, sepsis and diarrhea (5% each). Fatal adverse reactions occurred in 8% of patients, including acute kidney injury (2.2%), metabolic acidosis, sepsis, multiorgan dysfunction, pneumonia and pneumonitis (1.1% each). Adverse reactions leading to discontinuation occurred in 20% of patients; the most common (2%) was PN (7%). Adverse reactions leading to dose interruption occurred in 60% of patients; the most common (3%) were PN (19%), rash (9%), fatigue (8%), diarrhea (5%), AST increased and hyperglycemia (3% each). Adverse reactions leading to dose reduction occurred in 49% of patients; the most common (3%) were PN (19%), rash (11%) and fatigue (7%). Clinically relevant adverse reactions (<15%) include vomiting (13%), AST increased (12%), lipase increased (11%), ALT increased (10%), pneumonitis (4%) and infusion site extravasation (1%).

Drug Interactions

Effects of other drugs on PADCEV (Dual P-gp and Strong CYP3A4 Inhibitors)

Concomitant use with a dual P-gp and strong CYP3A4 inhibitors may increase unconjugated monomethyl auristatin E exposure, which may increase the incidence or severity of PADCEV toxicities. Closely monitor patients for signs of toxicity when PADCEV is given concomitantly with dual P-gp and strong CYP3A4 inhibitors.

Specific Populations

Lactation Advise lactating women not to breastfeed during treatment with PADCEV and for at least 3 weeks after the last dose.

Hepatic impairment Avoid the use of PADCEV in patients with moderate or severe hepatic impairment.

For more information, please see the full Prescribing Information including BOXED WARNING for PADCEV here.

About KEYTRUDA (pembrolizumab) injection, 100 mg

KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications in the U.S.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC):

Non-muscle Invasive Bladder Cancer

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

See additional selected KEYTRUDA indications in the U.S. after the Selected Important Safety Information.

Selected Important Safety Information for KEYTRUDA

Severe and Fatal Immune-Mediated Adverse Reactions

KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the PD-1 or the PD-L1, blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of antiPD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. For patients with TNBC treated with KEYTRUDA in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.

Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids were required in 69% (33/48); additional immunosuppressant therapy was required in 4.2% of patients. Colitis led to permanent discontinuation of KEYTRUDA in 0.5% (15) and withholding in 0.5% (13) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Colitis resolved in 85% of the 48 patients.

Hepatotoxicity and Immune-Mediated Hepatitis

KEYTRUDA as a Single Agent

KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 68% (13/19) of patients; additional immunosuppressant therapy was required in 11% of patients. Hepatitis led to permanent discontinuation of KEYTRUDA in 0.2% (6) and withholding in 0.3% (9) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Hepatitis resolved in 79% of the 19 patients.

KEYTRUDA With Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST) (13%) were seen at a higher frequency compared to KEYTRUDA alone. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. In patients with ALT 3 times upper limit of normal (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients who were rechallenged with either KEYTRUDA (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT 3 times ULN was observed in 1 patient receiving KEYTRUDA, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT 3 ULN subsequently recovered from the event.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.3%) reactions. Systemic corticosteroids were required in 77% (17/22) of patients; of these, the majority remained on systemic corticosteroids. Adrenal insufficiency led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.3% (8) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Hypophysitis

KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Hypophysitis occurred in 0.6% (17/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.2%) reactions. Systemic corticosteroids were required in 94% (16/17) of patients; of these, the majority remained on systemic corticosteroids. Hypophysitis led to permanent discontinuation of KEYTRUDA in 0.1% (4) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Thyroid Disorders

KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Thyroiditis occurred in 0.6% (16/2799) of patients receiving KEYTRUDA, including Grade 2 (0.3%). None discontinued, but KEYTRUDA was withheld in <0.1% (1) of patients.

Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent discontinuation of KEYTRUDA in <0.1% (2) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. Hypothyroidism occurred in 8% (237/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (6.2%). It led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.5% (14) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. The majority of patients with hypothyroidism required long-term thyroid hormone replacement. The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC, occurring in 16% of patients receiving KEYTRUDA as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in 389 adult patients with cHL (17%) receiving KEYTRUDA as a single agent, including Grade 1 (6.2%) and Grade 2 (10.8%) hypothyroidism.

Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic Ketoacidosis

Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA depending on severity. Type 1 DM occurred in 0.2% (6/2799) of patients receiving KEYTRUDA. It led to permanent discontinuation in <0.1% (1) and withholding of KEYTRUDA in <0.1% (1) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Immune-Mediated Nephritis With Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.1%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 89% (8/9) of patients. Nephritis led to permanent discontinuation of KEYTRUDA in 0.1% (3) and withholding in 0.1% (3) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Nephritis resolved in 56% of the 9 patients.

Immune-Mediated Dermatologic Adverse Reactions

KEYTRUDA can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with antiPD-1/PD-L1 treatments. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. Withhold or permanently discontinue KEYTRUDA depending on severity. Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 40% (15/38) of patients. These reactions led to permanent discontinuation in 0.1% (2) and withholding of KEYTRUDA in 0.6% (16) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 6% had recurrence. The reactions resolved in 79% of the 38 patients.

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received KEYTRUDA or were reported with the use of other antiPD-1/PD-L1 treatments. Severe or fatal cases have been reported for some of these adverse reactions. Cardiac/Vascular: Myocarditis, pericarditis, vasculitis; Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barr syndrome, nerve paresis, autoimmune neuropathy; Ocular: Uveitis, iritis and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; Gastrointestinal: Pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis (and associated sequelae, including renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% of 2799 patients receiving KEYTRUDA. Monitor for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion for Grade 1 or Grade 2 reactions. For Grade 3 or Grade 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after antiPD-1/PD-L1 treatments. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute and chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between antiPD-1/PD-L1 treatment and allogeneic HSCT. Follow patients closely for evidence of these complications and intervene promptly. Consider the benefit vs risks of using antiPD-1/PD-L1 treatments prior to or after an allogeneic HSCT.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with an antiPD-1/PD-L1 treatment in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-054, when KEYTRUDA was administered as a single agent to patients with stage III melanoma, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA. The most common adverse reaction (20%) with KEYTRUDA was diarrhea (28%). In KEYNOTE-716, when KEYTRUDA was administered as a single agent to patients with stage IIB or IIC melanoma, adverse reactions occurring in patients with stage IIB or IIC melanoma were similar to those occurring in 1011 patients with stage III melanoma from KEYNOTE-054.

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.

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Seagen, Astellas and Merck Announce Results of Clinical Trial Investigating PADCEV (enfortumab vedotin-ejfv) with KEYTRUDA (pembrolizumab) and PADCEV...