Archive for the ‘Bone Marrow Stem Cells’ Category

A new study from the Forsyth Institute is helping to shed light on latent tuberculosis and the bacteria's ability to hide in stem cells. Some bone marrow stem cells reside in low oxygen (hypoxia) zones. These specialized zones are secured as immune cells and toxic chemicals cannot reach this zone. Hypoxia- activated cell signaling pathways may also protect the stem cells from dying or ageing. A new study led by Forsyth Scientist Dr. Bikul Das has found that Mycobacterium tuberculosis (Mtb) hijack this protective hypoxic zone to hide intracellular to a special stem cell type. The study was published online on June 8th in the American Journal of Pathology.

Mtb, the causative organism of tuberculosis, infects nearly 2.2 billion people worldwide and causes 1.7 million annual deaths. This is largely attributed to the bacteria's ability to stay dormant in the human body and later resurface as active disease. Earlier research at Forsyth revealed that Mtb hides inside a specific stem cell population in bone marrow, the CD271+ mesenchymal stem cells. However, the exact location of the Mtb harboring stem cells was not known.

"From our previous research, we learned that cancer stem cells reside in the hypoxic zones to maintain self-renewal property, and escape from the immune system" said Bikul Das, MBBS, PhD, Associate Research Investigator at the Forsyth Institute, and the honorary director of the KaviKrishna laboratory, Guwahati, India. "So, we hypothesized that Mtb, like cancer, may also have figured out the advantage of hiding in the hypoxic area."

To test this hypothesis, Dr. Das and his collaborators at Jawarharlal Nehru Univeristy (JNU), New Delhi, and KaviKrishna Laboratory, Indian Institute of Technology, Guwahati, utilized a well-known mouse model of Mtb infection, where months after drug treatment, Mtb remain dormant for future reactivation. Using this mouse model of dormancy, scientists isolated the special bone marrow stem cell type, the CD271+ mesenchymal stem cells, from the drug treated mice. Prior to isolation of the stem cells, mice were injected with pimonidazole, a chemical that binds specifically to hypoxic cells. Pimonidazole binding of these cells was visualized under confocal microscope and via flow cytometry. The scientists found that despite months of drug treatment, Mtb could be recovered from the CD271+ stem cells. Most importantly, these stem cells exhibit strong binding to pimonidazole, indicating the hypoxic localization of the stem cells. Experiments also confirmed that these stem cells express a hypoxia activated gene, the hypoxia inducible factor 1 alpha (HIF-1 alpha).

To confirm the findings in clinical subjects, the research team, in collaboration with KaviKrishna Laboratory, the team isolated the CD271+ stem cell type from the bone marrow of TB infected human subjects who had undergone extensive treatment for the disease. They found that not only did the stem cell type contain viable Mtb, but also exhibit strong expression of HIF-1alpha. To their surprise, the CD271+ stem cell population expressed several fold higher expression of HIF-1alpha than the stem cell type obtained from the healthy individuals.

"These findings now explain why it is difficult to develop vaccines against tuberculosis," said Dr. Das. "The immune cells activated by the vaccine agent may not be able to reach the hypoxic site of bone marrow to target these "wolfs-in-stem-cell-clothing".

The success of this international collaborative study is now encouraging the team to develop a Forsyth Institute/KaviKrishna Laboratory global health research initiative to advance stem cell research and its application to global health issues including TB, HIV and oral cancer, all critical problems in the area where KaviKrishna Laboratory is located.

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Das is the co-senior and co-corresponding author of the study, Rakesh Bhatnagar, PhD, professor of biotechnology, JNU, New Delhi, is the co-senior author of the study. Ms. Jaishree Garhain, a PhD student of Dr. Das and Dr. Bhatnagar, is the first author of the study. Other members of the team are Ms. Seema Bhuyan, Dr. Deepjyoti Kalita, and Dr. Ista Pulu. The research was funded by the KaviKrishna Foundation (Sualkuchi, India), the Laurel Foundation (Pasadena, California), and Department of Biotechnology, India.

About The Forsyth Institute

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Tuberculosis bacteria hide in the low oxygen niches of ...

Bone Marrow Stem Cells

Dr. Steenblock performing a bone marrow stem cell treatment

The latest discovery in the world of natural medical therapies is STEM CELLS!

You have within you a powerful set of tools to repair your body and keep you healthy. The future of medicine is NOT better drugs but better use and application of your bodys own stem cells. As of now stem cell-rich tissue can be extracted from your hip with virtually no discomfort and used to help restore your body. This opens up an exciting new horizon in terms of preventing and treating disease and tackling the symptoms of aging if not aging itself. Already, patients are returning to Dr. Steenblock for additional bone marrow treatments because they are seeing that their gray or white hair is turning back to its original color. Their skin not infrequently looks younger too and they report having more energy and less arthritic aches and pains!

Over the past six years, Dr. Steenblock and his medical team have done over 2,000 bone marrow procedures with much success. Contrary to the conventional painful methods used, he and his colleagues have developed an almost painless approach to extract bone marrow and the hidden trove of stem cells contained within. Using the patients own bone marrow rather than someone elses has totally eliminated the risk of graft versus host disease and the need for toxic chemotherapy to suppress the immune system. Since Dr. Steenblock is merely transferring stem cells from a persons bones into their blood stream there is never an allergic or rejection type of reaction since these are the patients own cells. The results have at times been phenomenal especially for those under 40 and for those who are really physically fit and walk or run a lot every day. The stronger an individuals bones are the better the bone marrow stem cells are. Even children that are paralyzed and who do not put weight on their legs are generally not going to have good results unless add another facet is added to their treatment. For those people who do not walk much, are not physically fit and who are older than 40, Dr. Steenblock generally recommends that they undergo five successive daily injections of a natural bone marrow mobilizer called Neupogen (Filgrastim) beginning 19 days before they come to his office for their bone marrow treatment(s). The ideal treatment for anyone with a complicated health issue is to first have certain tests done to determine if they have any problems that could interfere with the treatments success. These tests include standard blood tests for anemia, hormones, metabolism, infections, autoimmunity, inflammation and special tests for heavy metal poisons and intestinal infections and infestations. If problems are discovered with these tests then the underlying problem should be corrected before beginning the process of using the Neupogen and the scheduling of the bone marrow treatment(s). The word marrows is pleural intentionally because a person in general has a better result if more stem cells are given. By having two bone marrow procedures on successive days an individual will double the number of stem cells they receive. For example, if a 60 year old sedentary person comes in and does only one bone marrow treatment Dr. Steenblock will generally extract about 400 milliliters of stem cell-rich bone marrow (buffy coat after centrifugation) which is put directly back into the blood stream by intravenous means. The number of active, healthy stem cells in this simple procedure may only be 100 million and these in general will not be as healthy or as active as they will be if the patient first has any known or potential impediments to their post-infusion activity eliminated and they are given the 5 daily injections of Neupogen. When a person comes to the clinic 14 days after their last Neupogen injection, that same 400 ml of bone marrow will have somewhere between 500 and 1000 million stem cells and then if they repeat the process the next day they will get another 500-1000 million stem cells. By this combination of eradicating infections, correcting other problems discovered using our testing, and then using Neupogen followed by two bone marrow treatments patients will be receiving well over a billion stem cells.

Benefits of Bone Marrow Stem Cells

What is the secret behind the successes Dr. Steenblock has seen with the bone marrow treatments? While bone marrow transplants have been done for the past 50 years for cancer patients and those with blood disorders, the whole bone marrow procedure done by Dr. Steenblock is different because it is so SIMPLE! He uses a persons own bone marrow and instead of isolating one type of stem cell, he takes and uses the whole raw bone marrow which contains a rich variety of stem and progenitor cells. In fact, bone marrow is rich in two different types of stem cells: One type turns into blood cells, blood vessels, and cells of the immune system and are called hematopoietic stem cells (heme meaning blood-related). The other type of stem cell is the support (stromal or mesenchymal) stem cell that produces bone, fat, tendons, skin, muscles and connective tissue. Recent research shows that these hematopoietic and the support stem cells are also able to divide into all types of brain cells, including glial cells (white matter) and neurons (gray matter). The bone marrow also contains retinal progenitor cells and several patients have actually commented on how their vision improved as a side benefit of their bone marrow procedure. These two type of stem cells work better together in a ratio of one hematopoietic to 4 to 8 support (stromal or mesenchymal) stem cells which is the ratio found normally in most peoples bone marrow.

In regard to its anti-aging effects, the bone marrow contains primitive progenitor cells that are associated with the early development of the fetus. These primitive cells reside dormant deep inside each of our bones and sport a virginal profile from early development in that these stem cells are generally resting and not active. This inactivity protects them from chemicals or stresses that induce mutations such as occurs in those bone marrow stem cells that are located in the more superficial areas of the bone which are constantly making red and white blood cells. When these primitive, more pure cells are released into a persons system, there can be a revitalization of the body that physiologically sets the clock back in-a-way since these stem cells get into all parts of the body and produce more growth factors than would otherwise be possible. It is this increase in growth factors that induces the regenerative processes. For those that can afford it Dr. Steenblock uses growth factors oriented toward improving the organs that are diseased. For example, if a patients chief problem is their lungs then he may suggest some lung growth factors to be taken right along with the Neupogen and then continued for 6 weeks to help push the stem cells into becoming more like lung tissue cells.

Bottom line: Bone marrow stem cells have the potential to repair damaged tissues and organs. Whether a person wants an anti-aging treatment or needs the procedure to repair damage in joints, liver, kidneys, heart or brain, bone marrow transplants is an efficient and sure way to flood their body with stem cells.

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bone marrow stem cells - Stem Cells Adult Stem Cells ...

Bone marrow stem cells

Diseases such as aplastic anaemia, or infections (such as tuberculosis) can negatively impact the ability of the bone marrow to produce blood cells or platelets. Other diseases, such as leukaemia, also affect the progenitor/stem cells in the bone marrow and are diagnosed by a bone marrow biopsy where a sample of the tissue is taken using a large hollow needle inserted into the iliac crest (the pelvic bone). Harvesting bone marrow is usually done under general anaesthetic, although local anaesthetic is also a possibility.

Recent advances in stimulating and harvesting stem cells from the peripheral blood may mean that the invasiveness of bone marrow harvesting can be avoided for some donors and patients. Stimulatory pharmaceuticals, such as GM-CSF, and G-CSF, which drive the stem cells out of the bone marrow and into the peripheral circulation, can allow for a large yield of stem cells during apheresis. However, bone marrow stem cells have been found through research in the past five years or so to be able to differentiate into more cell types than previously thought. Mesenchymal stem cells from bone marrow have been successfully cultured to create beta-pancreatic cells, and neural cells, with possible ramifications for treatment of diabetes and neurodegenerative diseases. Clinical trials involving stem cell treatments for such conditions in humans remain theoretical however as there are a number of issues that need further investigation to confirm efficacy and safety.

The stem cells contained within bone marrow are of three types; haematopoietic stem cells, mesenchymal stem cells, and endothelial stem cells. Haematopoietic stem cells differentiate into both white and red blood cells, and platelets. These leukocytes, erythrocytes, and thrombocytes, respectively, play a role in immune function, oxygen transportation, and blood-clotting and are destroyed by chemotherapy for cancers such as leukaemia. This is why bone marrow transplants can mean the difference between life and death for someone suffering from such a disease as it is vital to replace and repopulate the bone marrow with stem cells that can then create new blood- and immune-forming cells.

Mesenchymal stem cells are also found in the bone marrow and are responsible for creating osteoblasts, chrondrocytes, and mycocytes, along with a number of other cell types. The location of these stem cells differs from that of the haematopoietic stem cells as they are usually central to the bone marrow, which makes it easier to extract specific populations of stem cells during a bone marrow aspiration procedure.

Bone marrow mesenchymal stem cells have also been found to differentiate into beta-pancreatic islet cells, with potential ramifications for treating those with diabetes (Moriscot, et al, 2005). Neural-like cells have also been cultured from bone marrow mesenchymal stem cells making the bone marrow a possible source for stem cell treatment of neurological disorders (Hermann, et al, 2006). More recent research appears to show that donor-heterogeneity (genetic differences between those donating the bone marrow) is at the heart of the variability in mesenchymal stem cells ability to differentiate to neural cells (Montzka, et al, 2009). This means that careful selection of donor stem cells would have to be carried out in order for treatment to be successful if the research ever displays clinical significance. Conditions such as spinal cord injury, Alzheimers Disease, and Multiple Sclerosis, may be able to be treated in the future using mesenchymal stem cells from bone marrow that were previously thought to only be able to produce bone and cartilage cell types.

Patients with leukaemia or other cancer are likely to be treated with radiation and/or chemotherapy. Both of these treatements kill the stem cells in the bone marrow to some degree and it is the effect that this has on the immune system that is responsible for many of the symptoms of chemotherapy and radiation sickness. In some cases, a patient with cancer may have bone marrow harvested and some stem cells stored prior to radiation treatment or chemotherapy. They then have their own stem cells infused after the cancer treatment in order to repopulate their immune system. This presents little risk of graft versus host disease which is a concern with, non-autologous, allograft bone marrow transplants. The use of a patients own stem cells is unlikely to be helpful in cases where an in-borne mutation of the blood and lymph system is present and such procedures are not usually performed in such cases.

Bone marrow transplantation from a donor source will normally require the destruction of the patients own bone marrow in a process called myeloablation. Patients who undergo myeloablation will lose their acquired immunity and are usually advised to undergo all vaccinations for diseases such as mumps, measles, rubella, and so on. Myeloablation also means that the patient has extremely low white blood cell (leukocyte) levels for a number of weeks as the bone marrow stem cells begin to create new blood and immune system cells. Patients undergoing this procedure are, therefore, extremely susceptible to infection and complication making bone marrow transplants only appropriate in life-threatening situations. Many patients will take antibiotics during this time in an attempt to avoid sepsis, infections, and septic shock. Some patients will be given immunosuppressant drugs to lower the risk of graft versus host disease and this can make them even more susceptible to infection.

It is also possible that the new stem cells do not engraft, which means that they do not begin to create new blood and immune-system cells at all. Peripheral blood stem cells harvested at the same time as bone marrow harvesting were found in one study to speed the recovery of the patients immune systems following myeloablation, thus reducing the risk if infection (Rabinowitz, et al, 1993). Peripheral blood stem cells do appear to be quicker in general at engrafting and they may become more widely involved in the treatment of diseases traditionally addressed through bone marrow transplants (Lewis, 2005).

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Bone Marrow Stem Cells - Stem Cell Research

by Jos Domen*, Amy Wagers** and Irving L. Weissman***

Blood and the system that forms it, known as the hematopoietic system, consist of many cell types with specialized functions (see Figure 2.1). Red blood cells (erythrocytes) carry oxygen to the tissues. Platelets (derived from megakaryocytes) help prevent bleeding. Granulocytes (neutrophils, basophils and eosinophils) and macrophages (collectively known as myeloid cells) fight infections from bacteria, fungi, and other parasites such as nematodes (ubiquitous small worms). Some of these cells are also involved in tissue and bone remodeling and removal of dead cells. B-lymphocytes produce antibodies, while T-lymphocytes can directly kill or isolate by inflammation cells recognized as foreign to the body, including many virus-infected cells and cancer cells. Many blood cells are short-lived and need to be replenished continuously; the average human requires approximately one hundred billion new hematopoietic cells each day. The continued production of these cells depends directly on the presence of Hematopoietic Stem Cells (HSCs), the ultimate, and only, source of all these cells.

Figure 2.1. Hematopoietic and stromal cell differentiation.

2001 Terese Winslow (assisted by Lydia Kibiuk)

The search for stem cells began in the aftermath of the bombings in Hiroshima and Nagasaki in 1945. Those who died over a prolonged period from lower doses of radiation had compromised hematopoietic systems that could not regenerate either sufficient white blood cells to protect against otherwise nonpathogenic infections or enough platelets to clot their blood. Higher doses of radiation also killed the stem cells of the intestinal tract, resulting in more rapid death. Later, it was demonstrated that mice that were given doses of whole body X-irradiation developed the same radiation syndromes; at the minimal lethal dose, the mice died from hematopoietic failure approximately two weeks after radiation exposure.1 Significantly, however, shielding a single bone or the spleen from radiation prevented this irradiation syndrome. Soon thereafter, using inbred strains of mice, scientists showed that whole-body-irradiated mice could be rescued from otherwise fatal hematopoietic failure by injection of suspensions of cells from blood-forming organs such as the bone marrow.2 In 1956, three laboratories demonstrated that the injected bone marrow cells directly regenerated the blood-forming system, rather than releasing factors that caused the recipients' cells to repair irradiation damage.35 To date, the only known treatment for hematopoietic failure following whole body irradiation is transplantation of bone marrow cells or HSCs to regenerate the blood-forming system in the host organisms.6,7

The hematopoietic system is not only destroyed by the lowest doses of lethal X-irradiation (it is the most sensitive of the affected vital organs), but also by chemotherapeutic agents that kill dividing cells. By the 1960s, physicians who sought to treat cancer that had spread (metastasized) beyond the primary cancer site attempted to take advantage of the fact that a large fraction of cancer cells are undergoing cell division at any given point in time. They began using agents (e.g., chemical and X-irradiation) that kill dividing cells to attempt to kill the cancer cells. This required the development of a quantitative assessment of damage to the cancer cells compared that inflicted on normal cells. Till and McCulloch began to assess quantitatively the radiation sensitivity of one normal cell type, the bone marrow cells used in transplantation, as it exists in the body. They found that, at sub-radioprotective doses of bone marrow cells, mice that died 1015 days after irradiation developed colonies of myeloid and erythroid cells (see Figure 2.1 for an example) in their spleens. These colonies correlated directly in number with the number of bone marrow cells originally injected (approximately 1 colony per 7,000 bone marrow cells injected).8 To test whether these colonies of blood cells derived from single precursor cells, they pre-irradiated the bone marrow donors with low doses of irradiation that would induce unique chromosome breaks in most hematopoietic cells but allow some cells to survive. Surviving cells displayed radiation-induced and repaired chromosomal breaks that marked each clonogenic (colony-initiating) hematopoietic cell.9 The researchers discovered that all dividing cells within a single spleen colony, which contained different types of blood cells, contained the same unique chromosomal marker. Each colony displayed its own unique chromosomal marker, seen in its dividing cells.9 Furthermore, when cells from a single spleen colony were re-injected into a second set of lethally-irradiated mice, donor-derived spleen colonies that contained the same unique chromosomal marker were often observed, indicating that these colonies had been regenerated from the same, single cell that had generated the first colony. Rarely, these colonies contained sufficient numbers of regenerative cells both to radioprotect secondary recipients (e.g., to prevent their deaths from radiation-induced blood cell loss) and to give rise to lymphocytes and myeloerythroid cells that bore markers of the donor-injected cells.10,11 These genetic marking experiments established the fact that cells that can both self-renew and generate most (if not all) of the cell populations in the blood must exist in bone marrow. At the time, such cells were called pluripotent HSCs, a term later modified to multipotent HSCs.12,13 However, identifying stem cells in retrospect by analysis of randomly chromosome-marked cells is not the same as being able to isolate pure populations of HSCs for study or clinical use.

Achieving this goal requires markers that uniquely define HSCs. Interestingly, the development of these markers, discussed below, has revealed that most of the early spleen colonies visible 8 to 10 days after injection, as well as many of the later colonies, visible at least 12 days after injection, are actually derived from progenitors rather than from HSCs. Spleen colonies formed by HSCs are relatively rare and tend to be present among the later colonies.14,15 However, these findings do not detract from Till and McCulloch's seminal experiments to identify HSCs and define these unique cells by their capacities for self-renewal and multilineage differentiation.

While much of the original work was, and continues to be, performed in murine model systems, strides have been made to develop assays to study human HSCs. The development of Fluorescence Activated Cell Sorting (FACS) has been crucial for this field (see Figure 2.2). This technique enables the recognition and quantification of small numbers of cells in large mixed populations. More importantly, FACS-based cell sorting allows these rare cells (1 in 2000 to less than 1 in 10,000) to be purified, resulting in preparations of near 100% purity. This capability enables the testing of these cells in various assays.

Figure 2.2. Enrichment and purification methods for hematopoietic stem cells. Upper panels illustrate column-based magnetic enrichment. In this method, the cells of interest are labeled with very small iron particles (A). These particles are bound to antibodies that only recognize specific cells. The cell suspension is then passed over a column through a strong magnetic field which retains the cells with the iron particles (B). Other cells flow through and are collected as the depleted negative fraction. The magnet is removed, and the retained cells are collected in a separate tube as the positive or enriched fraction (C). Magnetic enrichment devices exist both as small research instruments and large closed-system clinical instruments.

Lower panels illustrate Fluorescence Activated Cell Sorting (FACS). In this setting, the cell mixture is labeled with fluorescent markers that emit light of different colors after being activated by light from a laser. Each of these fluorescent markers is attached to a different monoclonal antibody that recognizes specific sets of cells (D). The cells are then passed one by one in a very tight stream through a laser beam (blue in the figure) in front of detectors (E) that determine which colors fluoresce in response to the laser. The results can be displayed in a FACS-plot (F). FACS-plots (see figures 3 and 4 for examples) typically show fluorescence levels per cell as dots or probability fields. In the example, four groups can be distinguished: Unstained, red-only, green-only, and red-green double labeling. Each of these groups, e.g., green fluorescence-only, can be sorted to very high purity. The actual sorting happens by breaking the stream shown in (E) into tiny droplets, each containing 1 cell, that then can be sorted using electric charges to move the drops. Modern FACS machines use three different lasers (that can activate different set of fluorochromes), to distinguish up to 8 to 12 different fluorescence colors and sort 4 separate populations, all simultaneously.

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Key Messages:

Although a stem cell transplant (sometimes called a bone marrow transplant) is an effective treatment for several types of cancer, it can cause a number of different side effects. The type and intensity of these side effects vary from person to person and depend on the kind of transplant performed, the person's overall health, and other factors. Your health care team will work with you to prevent side effects or manage any that occur. This is called palliative or supportive care and is an important part of your overall treatment plan. Be sure to talk with your health care team about any side effects you experience, including new symptoms or a change in symptoms.

The two most serious side effects of stem cell transplantation are infection and graft-versus-host disease.

Infection

The chemotherapy and/or radiation therapy given before a stem cell transplant weakens a persons immune system, lowering the bodys defenses against bacteria, viruses, and fungi. That means stem cell recipients are especially vulnerable to infection during this early period of treatment.

Although most people think the greatest risk of infection is from visitors or food, most infections that occur during the first few weeks after a transplant are caused by organisms that are already in the patient's lungs, sinuses, skin, and intestines. Fortunately, most of these infections are relatively easy to treat with antibiotics.

The reduced immunity of the early transplant period lasts about two weeks, after which the immune system is back to near full strength and can keep most common germs at bay without the help of medications. This is true for both autologous (AUTO) transplant recipients (who receive their own stem cells) and allogeneic (ALLO) transplant recipients (who receive stem cells from another person).

However, a risk of serious infection remains for ALLO transplant recipients because they are given anti-rejection drugs. These drugs suppress the immune system to prevent the body from rejecting the donors stem cells. However, this low immunity also leaves the body more at risk for infection. This risk increases when more anti-rejection drugs are needed. Your treatment team will work with you to prevent and manage infections.

Graft-versus-host disease

People who have an ALLO transplant are also at risk of developing a post-transplant illness called graft-versus-host disease (GVHD). It occurs when the transplanted stem cells recognize the patients body as foreign and attack it, causing inflammation. GVHD ranges from mild to life-threatening. AUTO transplant recipients do not face this risk because the transplanted stem cells come from their own bodies.

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Side Effects of Stem Cell/Bone Marrow Transplantation ...

Repairing Chronic Muscle Tears with Stem Cells
Chronic muscle tears like hamstring pulls and shoulder rotator cuff muscles are tough to heal. Research suggests that injecting bone marrow stem cells into the area may solve that problem.

By: Chris Centeno

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Repairing Chronic Muscle Tears with Stem Cells - Video

What can mesenchymal stem cells do?

Mesenchymal stem cells (MSCs) are an example of tissue or 'adult' stem cells. They are multipotent, meaning they can produce more than one type of specialized cell of the body, but not all types. MSCs make the different specialized cells found in the skeletal tissues. For example, they can differentiate or specialize into cartilage cells (chondrocytes), bone cells (osteoblasts) and fat cells (adipocytes). These specialized cells each have their own characteristic shapes, structures and functions, and each belongs in a particular tissue.

Some early research suggested that MSCs might also differentiate into many different types of cells that do not belong to the skeletal tissues, such as nerve cells, heart muscle cells, liver cells and endothelial cells, which form the inner layer of blood vessels. These results have not been confirmed to date. In some cases, it appears that the MSCs fused together with existing specialized cells, leading to false conclusions about the ability of MSCs to produce certain cell types. In other cases, the results were an artificial effect caused by chemicals used to grow the cells in the lab.

Mesenchymal stem cell differentiation: MSCs can make fat, cartilage and bone cells. They have not been proven to make other types of cells of the body.

MSCs were originally found in the bone marrow. There have since been many claims that they also exist in a wide variety of other tissues, such as umbilical cord blood, adipose (fat) tissue and muscle. It has not yet been established whether the cells taken from these other tissues are really the same as, or similar to, the mesenchymal stem cells of the bone marrow.

The bone marrow contains many different types of cells. Among them are blood stem cells (also called hematopoietic stem cells; HSCs) and a variety of different types of cells belonging to a group called mesenchymal cells. Only about 0.001-0.01% of the cells in the bone marrow are mesenchymal stem cells.

It is fairly easy to obtain a mixture of different mesenchymal cell types from adult bone marrow for research. But isolating the tiny fraction of cells that are mesenchymal stem cells is more complicated. Some of the cells in the mixture may be able to form bone or fat tissues, for example, but still do not have all the properties of mesenchymal stem cells. The challenge is to identify and pick out the cells that can both self-renew (produce more of themselves) and can differentiate into three cell types bone, cartilage and fat. Scientists have not yet reached a consensus about the best way to do this.

No treatments using MSCs are yet available. However, several possibilities for their use in the clinic are currently being explored.

Bone and cartilage repair The ability of MSCs to differentiate into bone cells called osteoblasts has led to their use in early clinical trials investigating the safety of potential bone repair methods. These studies are looking at possible treatments for localized skeletal defects (damage at a particular place in the bone).

Other research is focussed on using MSCs to repair cartilage. Cartilage covers the ends of bones and allows one bone to slide over another at the joints. It can be damaged by a sudden injury like a fall, or over a long period by a condition like osteoarthritis, a very painful disease of the joints. Cartilage does not repair itself well after damage. The best treatment available for severe cartilage damage is surgery to replace the damaged joint with an artificial one. Because MSCs can differentiate into cartilage cells called chondrocytes, scientists hope MSCs could be injected into patients to repair and maintain the cartilage in their joints. Researchers are also investigating the possibility that transplanted MSCs may release substances that will tell the patients own cells to repair the damage.

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Mesenchymal stem cells: the 'other' bone marrow stem cells ...

Nichole Bushong shares her story of helping save someone elses live

J.O. PARKER joparker@registermedia.com

It was November 2013.

Nichole Bushong of Malcom received a phone call from the National Bone Marrow Donor Program.

She was a potential match for a bone marrow recipient, and the call came to ask if she would consider some initial blood tests to see if she might be a match.

Bushong, who owns Memories Maid in Grinnell, had signed on to the national registry in June 2013 after an uncles brother needed a transplant.

He ended up getting a transplant from another donor and is doing great now, recalled Bushong.

Bushong said some people on the registry wait years before receiving a call. In her case, it was just a few months.

Nichole Bushong is shown with her husband, Lucas, on their wedding day in August 2014. Bushong, along with Sam Coster, will be in Grinnell on Wednesday, April 22 to meet with local and area residents to talk about donating and signing up for the National Bone Marrow Registry. Courtesy Photo

A story of love

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Donating bone marrow was a piece of cake for Malcom woman

Next month Mr Brown and his wife will attend the wedding in the United States as very special guests.

He joined the Anthony Nolan register in the late 1980s when his baby son Michael - now 33 - was being treated for cancer.

A few years later, in 1991, he received a call to tell him that he was a match for a patient in the USA who was in desperate need of a transplant.

Mr Brown agreed to donate and travelled to the Harley Street Clinic in London to make the lifesaving donation.

He gave his bone marrow on the morning of May 17, 1991, and it was immediately picked up by a courier who flew over to the USA on Concorde, on a journey of more than 3,500 miles, which allowed the patient to have his transplant that evening.

Mr Brown said: It was so rewarding after making the donation, I went round with a huge smile on my face for six months.

Following the donation, the sales manager learned that his bone marrow had gone to a 44-year-old man called Rick Haines who lived in Delaware and who was suffering from aplastic anaemia.

Afterwards, Mr Haines, an engineer in the motor industry, contacted Mr Brown to thank him.

Mr Haines, now 68, explained that he had feared he would not live to see his young daughter walk down the aisle, and a deal was struck.

Donor organs from cancer patients should be transplanted despite risks

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Bone marrow donation ends in a wedding promise

Stem Cell Research in Cardiology
Bharat Book Bureau provides the report, on Stem Cell Research in Cardiology. The study is segmented by Source (Allogenic and Autogenic) and by Type (Bone Marrow Stem Cells, Embryonic...

By: Bharat Book

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Stem Cell Research in Cardiology - Video

Telomeres are short stretches of repeated nucleotides that protect the ends of chromosomes. In somatic cells, these protective sequences become shorter with each cellular replication until a critical length is reached, which can trigger cell death.

In actively replicating cells such as germ cells, embryonic stem cells, and blood stem cells of the bone marrow, the enzyme telomerase replenishes these protective caps to ensure adequate replication. Cancer cells also seem to have the ability to activate telomerase, which allows them to keep dividing indefinitely, with dire consequences for the patient. However, according to a study published April 10 in the JNCI: Journal of the National Cancer Institute, the extent to which cancer cells can utilize telomerase may depend on which variants of the genes related to telomerase activity are expressed in an individual's cells.

Telomere shortening is an inevitable, age-related process, but it can also be exacerbated by lifestyle factors such as obesity and smoking. Thus, some previous studies have found an association between short telomeres and high mortality, including cancer mortality, while others have not. A possible explanation for the conflicting evidence may be that the association found between short telomeres and increased cancer mortality was correlational but other factors (age and lifestyle), not adjusted for in previous studies, were the real causes. Genetic variation in several genes associated with telomere length (TERC, TERT, OBFC1) is independent of age and lifestyle. Thus, a genetic analysis called a Mendelian randomization could eliminate some of the confounding and allow the presumably causal association of telomere length and cancer mortality to be studied.

To perform this analysis, Line Rode, M.D., Ph.D., of the Department of Clinical Biochemistry and The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark, and colleagues, used data from two prospective cohort studies, the Copenhagen City Heart Study and the Copenhagen General Population Study, including 64,637 individuals followed from 1991-2011. Participants completed a questionnaire and had a physical examination and blood drawn for biochemistry, genotyping, and telomere length assays.

For each subject, the authors had information on physical characteristics such as body mass index, blood pressure, and cholesterol measurements, as well as smoking status, alcohol consumption, physical activity, and socioeconomic variables. In addition to the measure of telomere length for each subject, three single nucleotide polymorphisms of TERC, TERT, and OBFC1 were used to construct a score for the presence of telomere shortening alleles.

A total of 7607 individuals died during the study, 2420 of cancer. Overall, as expected, decreasing telomere length as measured in leukocytes was associated with age and other variables such as BMI and smoking and with death from all causes, including cancer. Surprisingly, and in contrast, a higher genetic score for telomere shortening was associated specifically with decreased cancer mortality, but not with any other causes of death, suggesting that the slightly shorter telomeres in the cancer patients with the higher genetic score for telomere shortening might be beneficial because the uncontrolled cancer cell replication that leads to tumor progression and death is reduced.

The authors conclude, "We speculate that long telomeres may represent a survival advantage for cancer cells, allowing multiple cell divisions leading to high cancer mortality."

###

Contact info:

Stig E. Bojesen, M.D., D.M.Sc., stig.egil.bojesen@regionh.dk

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Telomeres and cancer mortality: The long and the short of it

Frederick, MD (PRWEB) April 09, 2015

Based upon strong market demand, RoosterBio Inc has announced the commercial launch of RoosterVial-hBM-50M MSC, a single vial containing 50 million human bone-marrow derived mesenchymal stem/stromal cells. This unprecedented, ultra-high cell number product configuration enables Regenerative Medicine organizations to accelerate scale-up and product development activities. RoosterBios core technology, which includes cell and media systems, allows tissue engineers, biofabricators, 3D bioprinters and cell therapy developers to instantly scale up, using simplified and standardized methods.

The 50 million hMSC vial delivers immediate cell biomass without the need for prior expansion. This results in saving significant time, resources and expense during bioprocess scale-up optimization. Since the system contains the most well-characterized hMSCs available on the market, the industry is assured robust and reproducible results. As with other RoosterBio products, this 50 million cell product is capable of greater than 100-fold expansion (>5 billion cells) within two weeks when cultured in RoosterBio medium. Prior to this technology, obtaining such cell numbers so rapidly was virtually impossible.

RoosterBio continues to broaden their portfolio of product formats, providing solutions for an extensive range of Regenerative Medicine therapeutic categories. The evolving product portfolio enables researchers and product developers to perform small scale screening studies, large scale development studies, and now, scale-up manufacturing bioprocess experiments using the 50 million cell product. Rapid prototyping of 3D bioprinted tissues utilizing hMSCs as the primary component of the cellular bioink is also now achievable. The Company offers various product configurations including 1 million cell vials, 10 million cell vials, and high performance media systems, as well as pre-assembled working cell banks and kits for rapidly achieving stem cell biomass. Jon Rowley, CEO of RoosterBio stated: "The Industry has published a technology roadmap for scalable cell manufacturing and 3D bioprinting, yet the materials needed to test and implement these technologies are not readily available. RoosterBio is addressing this major roadblock with innovative product formats that enable users to do more work, faster, and with much less out-of-pocket expense."

RoosterBios mission is to accelerate the development and commercialization of Regenerative Medicine products, by providing standardized stem cell product platforms that enable rapid translation of discoveries into product development. For more information, please email Priya Baraniak at priya@roosterbio.com or phone 1-412-606-1160.

About RoosterBio

RoosterBio is a privately held biofabrication tools company focused on accelerating the development of a sustainable regenerative medicine industry, one customer at a time. RoosterBios products are high volume, affordable, and well-characterized adult human mesenchymal stem/stromal cells (hMSCs) paired with highly engineered media systems. RoosterBio has simplified and standardized how stem cells are purchased, expanded, and used in development, leading to marked time and costs savings for customers. RoosterBios innovative products are ushering in a new era of productivity and standardization into the field, where researchers spend newly found time and money performing more high-value experiments, accelerating the road to discovery in Regenerative Medicine. For more information on RoosterBio and adult stem cells, you can visit http://www.roosterbio.com, follow on twitter (@RoosterBio), or read the highly-acclaimed blog Democratizing Cell Technologies (http://www.roosterbio.blogspot.com).

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RoosterBio Inc. launches new stem cell product format enabling rapid, scalable cell manufacturing and 3D bioprinting

Rice University and Texas Children's Hospital scientists are using stem cells from amniotic fluid to promote the growth of robust, functional blood vessels in healing hydrogels.

In new experiments, the lab of bioengineer Jeffrey Jacot combined versatile amniotic stem cells with injectable hydrogels used as scaffolds in regenerative medicine and proved they enhance the development of vessels needed to bring blood to new tissue and carry waste products away.

The results appear in the Journal of Biomedical Materials Research Part A.

Jacot and his colleagues study the use of amniotic fluid cells from pregnant women to help heal infants born with congenital heart defects. Such fluids, drawn during standard tests, are generally discarded but show promise for implants made from a baby's own genetically matched material.

He contends amniotic stem cells are valuable for their ability to differentiate into many other types of cells, including endothelial cells that form blood vessels.

"The main thing we've figured out is how to get a vascularized device: laboratory-grown tissue that is made entirely from amniotic fluid cells," Jacot said. "We showed it's possible to use only cells derived from amniotic fluid."

In the lab, researchers from Rice, Texas Children's Hospital and Baylor College of Medicine combined amniotic fluid stem cells with a hydrogel made from polyethylene glycol and fibrin. Fibrin is a biopolymer critical to blood clotting, cellular-matrix interactions, wound healing and angiogenesis, the process by which new vessels branch off from existing ones. Fibrin is widely used as a bioscaffold but suffers from low mechanical stiffness and rapid degradation. Combining fibrin and polyethylene glycol made the hydrogel much more robust, Jacot said.

The lab used vascular endothelial growth factor to prompt stem cells to turn into endothelial cells, while the presence of fibrin encouraged the infiltration of native vasculature from neighboring tissue.

Mice injected with fibrin-only hydrogels showed the development of thin fibril structures, while those infused with the amniotic cell/fibrin hydrogel showed far more robust vasculature, according to the researchers.

Similar experiments using hydrogel seeded with bone marrow-derived mesenchymal cells also showed vascular growth, but without the guarantee of a tissue match, Jacot said. Seeding with endothelial cells didn't work as well as the researchers expected, he said.

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Amniotic stem cells demonstrate healing potential

Miami, FL (PRWEB) April 09, 2015

Global Stem Cells Group subsidiary Adimarket has been named the Latin America distributor for bone marrow technology leader Ranfac Corporation. The announcement coincides with Global Stem Cells Groups most recent expansion plans in Latin America, an ongoing effort to meet the regions growing demands for access to regenerative medicine and stem cell therapies.

Ranfac manufactures state-of-the-art surgical, radiology, hematology and orthopedic products including a range of bone marrow aspiration needles, each designed to provide a simple means of harvesting marrow from the patients sternum (breastbone) or the iliac crest (part of the pelvic bone) for a variety of medical procedures. Ranfacs newest technology is designed to harvest high quality bone marrow derived cells without the need for centrifugation.

Ranfac bone marrow technology is used by physicians and medical specialists worldwide. Global Stem Cells Group Advisory Board member Joseph Purita, M.D., a pioneer in the use of laser and stem cell therapies in orthopedic medicine, endorses Ranfacs bone marrow aspiration technology. Purita recently joined other specialists including fellow GSCG Advisory Board member David B Harrell, PhD, Brt, OF, FAARM, FRIPH, DABRM, in a trial study and white paper collaboration on Ranfacs new, non-centrifugal bone marrow technology.

Both Purita and Harrell endorse the Ranfac systems enhanced safety and ability to increase the concentrations of stem and progenitor cells during the bone marrow aspiration process.

Our ground-breaking hematology and orthopedic products for bone marrow access, aspiration, stem cell harvesting and biopsy procedures are designed to provide a more efficient result during critical procedures, says Ranfac CEO Barry Zimble. We believe that this is the perfect time to team with Global Stem Cells Group as our distribution partner in Latin Americas fast-growing medical community.

The collaboration between Global Stem Cells Group and Ranfac is another step toward GSCGs commitment to expanding its presence in communities that need and deserve access to cutting-edge regenerative medicine, not only in Latin America but also worldwide.

The timing couldnt be better to represent Ranfacs cutting edge bone marrow technology in the emerging markets of Latin America. Global is always looking to provide patients and practitioners with the best resources that regenerative medicine has to offer says Ricardo DeCubas, Global Stem Cells Group co-founder and Regenestem CEO.

For more information visit the Global Stem Cells Group website, email bnovas@stemcellsgroup.com, or call 305-224-1858.

About Global Stem Cells Group:

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Global Stem Cells Group Subsidiary Adimarket Named Latin American Distributor for Ranfac Bone Marrow Technology

With no match in the family, his doctors in Ahmedabad started scrounging for random donors across India. There are only four voluntary marrow donor registries in Delhi, Chennai and Mumbai.

Two years ago, 15-year-old blood cancer patient Bhargav Gajipara's parents were a worried lot. Doctors had given up all hope for his cure as no medicines would work on the cancer. The last resort, they said, was a bone marrow transplant. Bhargav was suffering from acute myeloid leukemia (AML), a condition in which cancerous white blood cells (WBCs) get generated in the bone marrow and circulate in the blood stream. Even as Bhargav had fever and bleeding, his search for a bone marrow match within his family failed. The chances of a bone marrow transplant for him looked bleak until May in 2013.

With no match in the family, his doctors in Ahmedabad started scrounging for random donors across India. There are only four voluntary marrow donor registries in Delhi, Chennai and Mumbai.

Life suddenly changed for Bhargav in July, when his bone marrow matched with hundred percent accuracy with that of 26-year-old media professional Sachin Mampatta of Mumbai. The chance of finding a random bone marrow donor match are one in over 10,000.

On Tuesday, Bhargav and Sachin met one year after the latter donated his marrow to the patient. Sachin had incidentally pledged his marrow around the same time when the request for procuring Bhargav's match was put in by doctors. "I became aware that people can pledge their marrow when I attended a marrow donor drive at Matunga. The doctors took a swab from my inner cheek and genetically typed it. A few months later I received a call asking if I would be in a position to donate my marrow to Bhargav. I readily agreed," said Sachin.

"Sachin's blood was taken and his stem cells were extracted from the bloodstream. The 220 ml of stem cell component was transported to the Ahmedabad-based hospital where Bhargava was admitted," said Raghu Rajagopal, CEO, Datri Blood Stem Cell Donors Registry.

The doctors administered injections to destroy all the WBCs in Bhargav's blood and transfused Sachin's stem cells in Bhargav's blood. Soon, his blood was free of cancerous cells.

Ashok spent Rs 25 lakhs for Bhargav's bone marrow transplant procedure and raised money by selling his ancestral land in Rajkot.

Datri has 80,000 voluntary donors who have pledged their marrow since 2009. But the demand for marrow is very high. Up to one lakh people get blood cancer every year, a sizeable chunk of whom can be cured only through bone marrow transplant. "We have up to 2,500 patients on list, waiting to receive bone marrow, but have not been able to find a match for them. We get 15-20 patients every day who enroll for want of marrow. Many patients die on waiting list. More Indians need to come up and pledge their bone marrow," said Rajagopal.

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A bone marrow transplant made them blood brothers

Kenneth Lau

Wednesday, April 08, 2015

The Chinese University and three mainland institutions have produced a new kind of "engineered bone" with blood vessels and nerve cells to help treat patients.

Joining the Chinese University in the HK$50 million-HK$60 million research were Fourth Military Medical University, Shanghai Jiao Tong University School of Medicine and the Southern Medical University Nan Fang Hospital.

Professor Li Gang of Chinese University's department of orthopedics and traumatology said the discovery accelerates the recovery rate and lessens the pain.

In the past, traditional engineered bone had been used to replace bone lost in accidents or removed, but the outcome was not good enough and the new bone did not grow properly.

Li said if blood vessels and nerve cells are implanted into the engineered bone, the new bone will grow better, though the end result is still under study. Hong Kong's public hospitals had yet to use the new technology as a human clinical application. This had so far only been done in the mainland.

Li believes the cost for surgery will range between HK$80,000 and HK$100,000. He called on the government to put more resources into the study.

The Chinese University has received eight awards this year, including two first-class awards and five second-class awards in natural sciences, as well as one first-class award in scientific and technological progress.

University vice chancellor Joseph Sung Jao-yiu and his research team also received a first- class award in natural sciences. His research topic was integrative research on molecular basis and potential diagnostic and therapeutic targets for colorectal cancer.

Originally posted here:
Team offers bone surgery hope

Normal doses of chemotherapy (chemo) can harm normal cells as well as cancer cells. A stem cell transplant offers doctors a way to use the very high doses of chemo needed to kill all the leukemia cells. Although the drugs destroy the patient's bone marrow, stem cells given after the chemo can restore the blood-making bone marrow stem cells. This is called a stem cell transplant (SCT).

These blood-forming stem cells can come from the bone marrow or peripheral blood from either the patient or from a donor whose tissue type closely matches that of the patient. For CML, a donor (or allogeneic) transplant is most often used. The donor may be a brother or sister or less often a person not related to the patient.

Before modern targeted therapy drugs like imatinib (Gleevec), SCT was commonly used to treat CML. Thats because before drugs like imatinib, less than half of patients lived more than 5 years after diagnosis. Now, these drugs are the standard treatment, and transplants are being used less often. Still, a SCT from a donor offers the only proven chance to cure this disease, and many doctors will recommend a transplant for younger patients, especially children. Transplant may also be recommended if the CML is not responding well to the new drugs.

For more information on stem cell transplants, see Stem Cell Transplant (Peripheral Blood, Bone Marrow, and Cord Blood Transplants).

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Bone marrow or peripheral blood stem cell transplant for ...

Chris Goodman said its one of the most rewarding things hes ever done.

His stem cells reside inthe blood of a woman hes never met.

Goodman, a junior at Western Kentucky University, is working with a drive sponsored byWKU Greek Life and WKU student-athletesto register people for potential bone marrow donations. Donated stem cells, which are extracted from bone marrow, can be used to help people recover from serious illnesses.

The drive is April 20-22 at Raymond B. Preston Health and Activities Center. The hours are from 10 a.m. to 6 p.m.April 20 and 21 and from 10 a.m.to 7 p.m.April 22 in the Blue Court. Goodman will be working at the drive April 21, he said.

Goodman, 20, is from Knoxville, Tenn., and is a backstroke swimmer for WKU. Hes studying speech pathology and communications disorders and wants someday to work with kids who have speech difficulties.

A five-minute swab of your cheek could help save a life, Goodman said.

Goodman received a short note from the woman who was helped by his donation.

The letter I received from my patient was one which was very short in length but nonetheless very impactful, he said in an email. She and her family were very grateful that a complete stranger would give so much to someone they dont know.

His journey to becoming a bone marrow donator began when he registered withDelete Blood Cancer DKMSas a potential donor in April 2013. In October, Delete Blood Cancer sent him to Washington, D.C., and he donated stem cells during a five-day process.

He watched movies while sitting in his hospital bed as the procedure occurred. Having never even given a blood donation before, Goodman said the process did leave him a bit weak, although he participated in a swim meet for WKU within a week following the procedure, he said.

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WKU plans bone marrow registry drive

LOS ANGELES (KABC) --

While Roeuy Garay was pregnant with her daughter Brook, she felt weak and an unusual back pain. Her doctors thought it was just part of the pregnancy. But a few weeks after her delivery, her fiance Joseph knew something was seriously wrong.

"I passed out and he took me to urgent care and said, 'Something is wrong with her. It's got to be her kidney or something. We need to do some blood tests,'" Roeuy said.

A bone biopsy and body scan revealed a diagnosis the 36-year-old Corona mother of four could not believe.

"They came in and said, 'Yeah, you have multiple myeloma, and it's about between 70 to 80 percent of your blood is cancer,'" she said.

Multiple myeloma, also called Kahler's disease, is a cancer of the plasma cells, which are in the blood stream. Her best chance at survival is a bone marrow transplant.

None of her siblings were a match and being of Cambodian descent, Roeuy's odds of finding a match are very slim. It's a fact that is hard to hide from her children.

There are 12 million people in the National Bone Marrow Registry, but only 7 percent are Asian and only a small fraction of that are Southeast Asian.

Dr. Elizabeth Budde with City of Hope National Medical Center in Duarte said it only takes a cheek swab to be part of the registry and donating stem cells can be as easy as donating blood.

For now, Roeuy is in remission so she needs a match as soon as possible.

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Mother of 4 seeks bone marrow match

LOS ANGELES (KABC) --

While Roeuy Garay was pregnant with her daughter Brook, she felt weak and an unusual back pain. Her doctors thought it was just part of the pregnancy. But a few weeks after her delivery, her fiance Joseph knew something was seriously wrong.

"I passed out and he took me to urgent care and said, 'Something is wrong with her. It's got to be her kidney or something. We need to do some blood tests,'" Roeuy said.

A bone biopsy and body scan revealed a diagnosis the 36-year-old Corona mother of four could not believe.

"They came in and said, 'Yeah, you have multiple myeloma, and it's about between 70 to 80 percent of your blood is cancer,'" she said.

Multiple myeloma, also called Kahler's disease, is a cancer of the plasma cells, which are in the blood stream. Her best chance at survival is a bone marrow transplant.

None of her siblings were a match and being of Cambodian descent, Roeuy's odds of finding a match are very slim. It's a fact that is hard to hide from her children.

There are 12 million people in the National Bone Marrow Registry, but only 7 percent are Asian and only a small fraction of that are Southeast Asian.

Dr. Elizabeth Budde with City of Hope National Medical Center in Duarte said it only takes a cheek swab to be part of the registry and donating stem cells can be as easy as donating blood.

For now, Roeuy is in remission so she needs a match as soon as possible.

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Corona mother of 4 seeks bone marrow match

Children's Healthcare of Atlanta and Winship Cancer Institute target graft-versus-host-disease through immune cell therapy

An innovative clinical trial using the science of "personalized" cellular therapy has begun enrolling children and adults suffering from graft-versus-host-disease (GVHD), a life-threatening complication of bone marrow transplantation in which donor immune lymphocytes attack the organs of the bone marrow transplant recipient.

Bone marrow transplantation is performed in some patients with cancers of the blood or bone marrow, including multiple myeloma and leukemia, as well as in some patients with sickle cell disease, thallesemia, aplastic anemia and inherited immune deficiency.

Physician-researchers at the Aflac Cancer and Blood Disorders Center at Children's Healthcare of Atlanta and Winship Cancer Institute of Emory University will harvest bone marrow cells from children and adults (12 to 65 years) with GVHD. Those cells will be used to manufacture large numbers of personalized autologous marrow mesenchymal stromal cells in the Emory Personalized Immunotherapy Center (EPIC), a dedicated pharmaceutical grade facility located within Emory University Hospital.

By infusing large doses of these personalized bone marrow cells into bone marrow transplant recipients, the physician-researchers aim to target sites of inflammation, potentially reducing GVHD in the intestine, liver and skin and limiting long-term organ damage.

Muna Qayed, MD, MSc. a pediatric hematologist-oncologist at the Aflac Cancer Center at Children's and an assistant professor at Emory School of Medicine, will lead the clinical trial, which is offered only in Atlanta and is supported by CURE Childhood Cancer.

"For patients with GVHD who do not respond to first line therapy, there is no reliable cure, and GVHD can be life threatening or a life-long disabling condition," says Dr. Qayed, "But we hope that through our clinical research, we will be able to significantly impact the course of this disease."

"This trial represents one of the most innovative clinical trials to arise from the growing partnership between the Hematology & Medical Oncology and Pediatrics departments at Emory School of Medicine, Emory Healthcare, and Children's Healthcare of Atlanta," says William (Bill) G. Woods, MD, director of the Aflac Cancer Center.

Blood and bone marrow cells have been used for more than a quarter century to treat life-threatening hematological conditions and are now used in established therapies worldwide. The current clinical trial will use mesenchymal stromal cells from the bone marrow. These cells have been studied more recently for treatment of a wide array of diseases, including autoimmune diseases.

"The beginning of this clinical trial is the culmination of two years' of collaborative effort by a terrific multidisciplinary team at Emory Healthcare, Children's Healthcare of Atlanta and the Aflac Cancer Center," says Edmund Waller, MD, director of Winship's Bone Marrow and Stem Cell Transplant Program and investigator on this trial.

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Clinical trial uses patients' own cells for treatment after bone marrow transplant

This Saturday when the University of Kentucky basketball team faces off with the University of Wisconsin in the NCAA tournament semi-finals, die-hard Kentucky fan Scott Logdon may think twice about rooting against the Wisconsin Badgers.

Nearly two years ago, Logdon was given a life-saving donation of stem cells that helped combat his acute myeloid leukemia. The donor of those cells turned out to be 22-year-old Chris Wirz, a student at the University of Wisconsin.

Logdon, 44, learned the identity of his donor last April, more than a year after the stem cell treatment and just days after the University of Kentucky squeaked past the University of Wisconsin at the NCAA semi-finals with a score of 74 to 73.

Logdon remembers feeling mixed emotions when the Kentucky wildcats won. Later, when he found out about his donor, he joked, That must have been the Badger blood in me.

Courtesy Angela Logdon

PHOTO: Chris Wirz gave life saving stem cells to Scott Logdon, who was suffering from leukemia.

Logdons ordeal started in the fall of 2012, when he was diagnosed with acute myeloid leukemia after mistaking early symptoms for strep throat. Logdon said his doctors told him chemotherapy could only keep the cancer at bay. A full stem cell transplant would be needed to cure him of the deadly disease.

Logdons doctors hoped one of his two siblings might be a match, but neither was able to donate. Longons family and community rallied in the small town of Saldasia, Kentucky, and registered over 120 people who would be willing to donate stem cells or bone marrow.

But no one who registered was a good match for Logdon.

[The doctors] went to the national bone marrow registry to try and find the match, the father of four said. I had to go back to the hospital every 30 days [for] maintenance chemo; it was a very long wait.

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Kentucky Fan Gets Life-Saving Stem Cell Donation From Univ. of Wisconsin Student

CHICAGO, April 2, 2015 /PRNewswire-USNewswire/ --After surgery failed to relieve extreme pain caused by peripheral artery disease in her right leg, Denise Hopkins-Glover was facing a bleak outlook she might never walk again.

"They said they had done everything they could and the only option was amputation of the right leg from the knee down," she said.

Undeterred, Hopkins-Glover chose to participate in an investigational trial at Northwestern Medicine called the MOBILE Study, which makes use of a device called the MarrowStim PAD Kit. In the trial, a randomized group of patients receive injections of their own stem cells retrieved through a bone marrow extraction to try to restore blood flow to the leg.

"MarrowStim offers a new approach for patients with a grim prognosis," said principal investigator Melina Kibbe, MD, a vascular surgeon at Northwestern Memorial Hospital and Edward G. Elcock Professor of Surgical Research at Northwestern University Feinberg School of Medicine. "We're pleased to be part of this national trial to see if there might be a significant chance of improving treatment for patients with few choices left for treatment."

Hopkins-Glover, a 55-year-old grandmother of two, suffers from peripheral artery disease (PAD), a condition affecting 20 percent of Americans where cholesterol and fatty plaque pool in blood vessels, restricting blood flow to the limbs. In its most severe form, PAD causes critical limb ischemia (CLI), which can cause pain in resting legs, sores or ulcers that don't heal, thickening of the toenails and gangrene, which can eventually lead to amputation.

The Chicago resident worked as a phlebotomist before her PAD worsened, and had to stop working because she could no longer walk or stand for extended stretches of time.

"I can walk only a certain distance before the circulation stops getting to certain parts of the body," she said. "It feels like a terrible leg cramp, like a jabbing, stabbing pain."

During the procedure, patients are put under general anesthesia as bone marrow is harvested through a needle from the hip. The bone marrow is loaded into the MarrowStim PAD Kit, an investigational device, where it is processed in a centrifuge. This spinning separates the marrow into different layers, with one of the layers containing the stem cells. Immediately following the separation, the stem cells are injected in 40 different spots on the affected limb, delivering concentrated bone marrow in each one. The entire procedure takes about 90 minutes. Patients follow up with investigators at different intervals in the year following the injections.

Karen Ho, MD, a Northwestern Medicine vascular surgeon who is also an investigator on the trial, said the exact reason the bone marrow injections might help chronic limb ischemia is still a mystery.

"Nobody really knows the exact mechanism," said Dr. Ho, who is also an assistant professor in vascular surgery at Feinberg. "The idea is that it might improve or enhance new blood vessels in the calf."

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Northwestern Medicine Investigates Using Stem Cells to Save Limbs from Amputation

Low doses of the anti-cancer drug imatinib can spur the bone marrow to produce more innate immune cells to fight against bacterial infections, Emory researchers have found.

The results were published March 30, 2015 in the journal PLOS Pathogens.

The findings suggest imatinib, known commercially as Gleevec , or related drugs could help doctors treat a wide variety of infections, including those that are resistant to antibiotics, or in patients who have weakened immune systems. The research was performed in mice and on human bone marrow cells in vitro, but provides information on how to dose imatinib for new clinical applications.

"We think that low doses of imatinib are mimicking 'emergency hematopoiesis,' a normal early response to infection," says senior author Daniel Kalman, PhD, professor of pathology and laboratory medicine at Emory University School of Medicine.

Imatinib, is an example of a "targeted therapy" against certain types of cancer. It,blocks tyrosine kinase enzymes, which are dysregulated in cancers such as chronic myelogenous leukemia and gastrointestinal stromal tumors.

Imatinib also inhibits normal forms of these enzymes that are found in healthy cells. Several pathogens - both bacteria and viruses - exploit these enzymes as they transit into, through, or out of human cells. Researchers have previously found that imatinib or related drugs can inhibit infection of cells by pathogens that are very different from each other, including tuberculosis bacteria and Ebola virus.

In the new PLOS Pathogens paper, Emory investigators show that imatinib can push the immune system to combat a variety of bacteria, even those that do not exploit Abl enzymes. The drug does so by stimulating the bone marrow to make more neutrophils and macrophages, immune cells that are important for resisting bacterial infection.

"This was surprising because there are reports that imatinib can be immunosuppressive in some patients," Kalman says. "Our data suggest that at sub-clinical doses, imatinib can stimulate bone marrow stem cells to produce several types of myeloid cells, such as neutrophils and macrophages, and trigger their exodus from the bone marrow. However, higher doses appear to inhibit this process."

The authors note that imatinib appears to stimulate several types of white blood cells, which may provide a limit on inflammation, rather than increasing neutrophils only, which can be harmful. The authors go on to suggest that imatinib or related drugs may be useful in treating a variety of infections in patients whose immune system is compromised, such as those receiving chemotherapy for cancer.

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Originally posted here:
Anticancer drug can spur immune system to fight infection

Scott Logdon is a die-hard University of Kentucky basketball fan, but he can't deny he's got some Wisconsin blood in him -- literally.

When the father of four was being treated for high-risk leukemia at UK in 2013, 20-year-old University of Wisconsin student Chris Wirz anonymously donated bone marrow stem cells to him. The two men first spoke just after the Wildcats bested the Badgers during last year's NCAA Final Four, and basketball was a frequent topic of conversation as their friendship grew.

While each will be rooting for his own team during this Saturday's Final Four rematch, both say they have a soft spot for the other team.

"I've stayed true to UK," said Logdon, 44, of Salvisa, Ky. "But when I talked to Chris for the first time I told him, 'That's why I felt so bad when we beat you: I've got Badger blood in me!"'

Wirz, who lives three blocks from where the Badgers play, hopes Wisconsin wins this year, and has even predicted an upset in his basketball bracket. "Who doesn't want to root for the underdog?" he said.

But he plans to send a text of congratulations if Logdon's team wins -- since their connection is much deeper than basketball rivalry.

"We're literally working off the same immune system," said Wirz, now 22 and a University of Wisconsin senior. "This has been one of the most emotionally overwhelming experiences of my life, realizing how important he is to his family and his community and seeing the hole that would've been left by him."

A dire diagnosis

Logdon, chief deputy at Woodford County Detention Center in Versailles, Ky., and a youth minister in his church, recalled playing basketball with teenagers just a few nights before going to the doctor for what his wife, Angela, initially thought was strep.

But tests showed he had acute myeloid leukemia, a blood cancer estimated by the American Cancer Society to have stricken 18,860 Americans last year and killed about 10,460, mostly adults.

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Blood ties: Ky. basketball fan gets Wisconsin assist