Archive for the ‘IPS Cell Therapy’ Category

June 5, 2014

Nathan Hurst, University of Missouri

One of the biggest challenges for medical researchers studying the effectiveness of stem cell therapies is that transplants or grafts of cells are often rejected by the hosts. This rejection can render experiments useless, making research into potentially life-saving treatments a long and difficult process. Now, researchers at the University of Missouri have shown that a new line of genetically modified pigs will host transplanted cells without the risk of rejection.

The rejection of transplants and grafts by host bodies is a huge hurdle for medical researchers, said R. Michael Roberts, Curators Professor of Animal Science and Biochemistry and a researcher in the Bond Life Sciences Center. By establishing that these pigs will support transplants without the fear of rejection, we can move stem cell therapy research forward at a quicker pace.

In a published study, the team of researchers implanted human pluripotent stem cells in a special line of pigs developed by Randall Prather, an MU Curators Professor of reproductive physiology. Prather specifically created the pigs with immune systems that allow the pigs to accept all transplants or grafts without rejection. Once the scientists implanted the cells, the pigs did not reject the stem cells and the cells thrived. Prather says achieving this success with pigs is notable because pigs are much closer to humans than many other test animals.

Many medical researchers prefer conducting studies with pigs because they are more anatomically similar to humans than other animals, such as mice and rats, Prather said. Physically, pigs are much closer to the size and scale of humans than other animals, and they respond to health threats similarly. This means that research in pigs is more likely to have results similar to those in humans for many different tests and treatments.

Now that we know that human stem cells can thrive in these pigs, a door has been opened for new and exciting research by scientists around the world, Roberts said. Hopefully this means that we are one step closer to therapies and treatments for a number of debilitating human diseases.

Roberts and Prather published their study, Engraftment of human iPS cells and allogeneic porcine cells into pigs with inactivated RAG2 and accompanying severe combined immunodeficiency in the Proceedings of the National Academy of Sciences.

Source: Nathan Hurst, University of Missouri

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Stem Cells Successfully Transplanted And Grown In Pigs

This post is sponsored by DIA.

Regenerative medicines and the latest regulatory issues surrounding them will be a hot topic for discussion at the DIA 2014 50th Annual Meeting. This years Annual Meeting will be in San Diego from June 15 to 19 and will feature a session titled Pioneering Regenerative Medicine: Trends in Regulations for New Therapy, under the Nonclinical and Translational Development/Early Phase Clinical Development track.

The session, to be held on June 16 from 8:30-10:00 AM, will introduce the first clinical research of induced pluripotent stem (iPS) cell products in Japan and review the current regulatory status and governmental efforts surrounding regenerative medicine. Speakers will also identify issues in the application of the new technology and discuss possible solutions.

iPS cells hold great promise in the field of regenerative medicine because they can propagate indefinitely, as well as give rise to every other cell type in the body such as neurons, heart, pancreatic, and liver cells, and therefore represent a single source of cells that could be used to replace those lost to damage or disease. iPS cell technology was pioneered by Shinya Yamanaka of Kyoto, Japan, who was awarded the 2012 Nobel Peace Prize for the discovery alongside Sir John Gurdon.

The session will be chaired by Shinji Miyake, PhD, Professor of the Center for Clinical Research at Keio University School of Medicine in Japan.

The DIA 2014 50th Annual Meeting: Celebrate the Past Invent the Future is the largest multidisciplinary event that brings together a community of life sciences professionals at all levels and across all disciplines involved in the discovery, development, and life cycle management of medical products all with a common goal to foster innovation that will lead to the development of safe and effective medical products and therapies to patients.

This years event celebrates DIAs 50th Anniversary and will feature 260+ educational offerings over 21 tracks, 450+ exhibiting companies, over 125 representatives from global regulatory agencies, and much more. The meeting provides participants with a valuable opportunity to network with professionals from around the world, share knowledge, and build new relationships.

Find out more about DIA 2014 50th Annual Meeting at http://www.diahome.org/DIA2014.

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Introducing pioneering regenerative medicine

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Newswise CAMBRIDGE, Mass. (May 15, 2014) By studying nerve and liver cells grown from patient-derived induced pluripotent stem cells (iPSCs), Whitehead Institute researchers have identified a potential dual-pronged approach to treating Niemann-Pick type C (NPC) disease, a rare but devastating genetic disorder.

According to the National Institutes of Health (NIH), approximately 1 in 150,000 children born are afflicted with NPC, the most common variant of Niemann-Pick. Children with NPC experience abnormal accumulation of cholesterol in their liver and nerve cells, leading to liver failure, neurodegeneration, andultimatelydeath, often before age 10.

Although there is currently no effective treatment for NPC disease, a clinical trial examining potential cholesterol-lowering effects of the drug cyclodextrin in NPC patients is ongoing. However, research in Whitehead Founding Member Rudolf Jaenischs lab led by Dorothea Matezel along with Sovan Sarkar suggests that the high doses may actually be harmful. This and other findings are reported this week in the journal Stem Cell Reports.

At those levels of cyclodextrin (in the clinical trial), Maetzel and her coauthors show that cells encounter a further block in autophagy that could be detrimental, says Jaenisch, who is also a professor of biology at Massachusetts Institute of Technology. But when they use it at a lower dose in combination with another small molecule, carbamazepine, which stimulates autophagy, then it significantly improves the survival of the cells. Such an approach lowers cholesterol levels and restores the autophagy defects at the same time. This could be a new type of treatment for NPC disease.

To clarify what is amiss in NPC and identify potential therapeutics that could correct these problems, Maetzel generated iPSCs from patients with the most common genetic mutation that causes NPC. She created the iPSCs by pushing skin cells donated by the patients back to an embryonic stem cell-like state. These iPSCs were differentiated into liver and neuronal cells, the cell types most affected in NPC. Along with Haoyi Wang, a postdoctoral researcher in the Jaenisch lab, she then corrected one copy of the causal mutation, in the NPC1 gene, to create control cells whose genomes differ only at the single edited gene copy.

When Maetzel and Sarkar analyzed the cellular functions in the NPC1-mutant and control cell lines, they determined that although cholesterol does build up in the NPC1-mutant cells, a more significant problem is defective autophagya basic cellular function that degrades and recycles unneeded or faulty molecules, components, or organelles in a cell. The impaired autophagy prevents normal elimination of its cargo, such as damaged organelles or other substrates like p62, which then accumulates and damages the cells. The finding confirms previous work from the Jaenisch lab linking the NPC1 mutation to defective autophagy in mouse cells.

Autophagy dysfunction has major implications in several neurodegenerative and certain liver conditions, and therefore autophagy modulators have tremendous biomedical relevance, says Sarkar. We wanted to screen for compounds stimulating autophagy in human disease-relevant cells and show the beneficial effects of such an approach in the context of a lipid/lysosomal storage disorder.

Maetzel and Sarkar used the two types of human disease-affected cells to screen for compounds known to improve autophagy but not impacting on the mammalian target of rapamycin (mTOR) pathway, which has critical cellular functions and also controls autophagy. They found only one capable of jumpstarting autophagy independently of mTOR in both liver and nerve cells. When this drug, carbamazepine, which is a mood stabilizer prescribed for bipolar disorder, was added in combination with low doses of cyclodextrin, both cholesterol accumulation and autophagy defects were rescued in the NPC-mutated cells.

Continue reading here:
Combination Therapy a Potential Strategy for Treating Niemann Pick Disease

New York, NY (PRWEB) April 29, 2014

The Stem Cell Institute located in Panama City, Panama, welcomes special guest speaker Roberta F. Shapiro, DO, FAAPM&R to its public seminar on umbilical cord stem cell therapy on Saturday, May 17, 2014 in New York City at the New York Hilton Midtown from 1:00 pm to 4:00 pm.

Dr. Shapiro will discuss A New York Doctors Path to Panama.

Dr. Shapiro operates a private practice for physical medicine and rehabilitation in New York City. Her primary professional activities include outpatient practice focused on comprehensive treatment of acute and chronic musculoskeletal and myofascial pain syndromes using manipulation techniques, trigger point injections, tendon injections, bursae injections, nerve and motor point blocks. Secondary work at her practice focuses on the management of pediatric onset disability.

She is the founder and president of the Dayniah Fund, a non-profit charitable foundation formed to support persons with progressive debilitating diseases who are faced with catastrophic events such as surgery or illness. The Dayniah Fund educates the public about the challenges of people with disabilities and supports research on reducing the pain and suffering caused by disabling diseases and conditions.

Dr. Shapiro serves as assistant clinical professor in the Department of Rehabilitation and Regenerative Medicine at Columbia University Medical Center.

Stem Cell Institute Speakers include:

Neil Riordan PhD Clinical Trials: Umbilical Cord Mesenchymal Stem Cell Therapy for Autism and Spinal Cord Injury

Dr. Riordan is the founder of the Stem Cell Institute and Medistem Panama Inc.

Jorge Paz-Rodriguez MD Stem Cell Therapy for Autoimmune Disease: MS, Rheumatoid Arthritis and Lupus

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department IPS Cell Therapy IPS Cell Therapy

Cell lines made by two separate teams could boost the prospects of patient-specific therapies

This colony of embryonic stem cells, created from a type 1 diabetes patient, is one of the first to be cloned from an adult human. Credit:Bjarki Johannesson, NYSCF

Two research groups have independently produced human embryonic stem-cell lines from embryos cloned from adult cells. Their success could reinvigorate efforts to use such cells to make patient-specific replacement tissues for degenerative diseases, for example to replace pancreatic cells in patients with type 1 diabetes. But further studies will be needed before such cells can be tested as therapies.

The first stem-cell lines from cloned human embryos were reported in May last year by a team led by reproductive biology specialist Shoukhrat Mitalipov of the Oregon Health & Science University in Beaverton (see 'Human stem cells created by cloning'). Those cells carried genomes taken from fetal cells or from cells of an eight-month-old baby, and it was unclear whether this would be possible using cells from older individuals. (Errors were found in Mitalipov's paper, but were not deemed to affect the validity of its results.)

Now two teams have independently announced success. On 17 April, researchers led by Young Gie Chung and Dong Ryul Lee at the CHA University in Seoul reported inCell Stem Cellthat they had cloned embryonic stem-cell (ES cell) lines made using nuclei from two healthy men, aged 35 and 75. And in a paper published onNature's website today, a team led by regenerative medicine specialist Dieter Egli at the New York Stem Cell Foundation Research Institute describes ES cells derived from a cloned embryo containing the DNA from a 32-year-old woman with type 1 diabetes. The researchers also succeeded in differentiating these ES cells into insulin-producing cells.

Nuclear transfer To produce the cloned embryos, all three groups used an optimized version of the laboratory technique called somatic-cell nuclear transfer (SCNT), where the nucleus from a patient's cell is placed into an unfertilized human egg which has been stripped of its own nucleus. This reprograms the cell into an embryonic state. SCNT was the technique used to create the first mammal cloned from an adult cell, Dolly the sheep, in 1996.

The studies show that the technique works for adult cells and in multiple labs, marking a major step. It's important for several reasons, says Robin Lovell-Badge, a stem-cell biologist at the MRC National Institute for Medical Research in London.

At present, studies to test potential cell therapies derived from ES cells are more likely to gain regulatory approval than those testing therapies derived from induced pluripotent stem (iPS) cells, which are made by adding genes to adult cells to reprogram them to an embryonic-like state. Compared with iPS cells, ES cells are less variable, says Lovell-Badge. Therapies for spinal-cord injury and eye disease using non-cloned ES cells have already been tested in human trials. But while many ES cell lines have been made using embryos left over from fertility treatments, stem cells made from cloned adult cells are genetically matched to patients and so are at less risk of being rejected when transplanted.

Ethically fraught Lovell-Badge says cloned embryos could also be useful in other ways, in particular to improve techniques for reprogramming adult cells and to study cell types unique to early-stage embryos, such as those that go on to form the placenta.

Few, however, expect a huge influx of researchers making stem cells from cloned human embryos. The technique is expensive, technically difficult and ethically fraught. It creates an embryo only for the purpose of harvesting its cells. Obtaining human eggs also requires regulatory clearance to perform an invasive procedure on healthy young women, who are paid for their time and discomfort.

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Stem Cells Made from Cloned Human Embryos

Regenerative medicine took a step forward on Monday with the announcement of the creation of the first disease-specific line of embryonic stem cells made with a patient's own DNA.

These cells, which used DNA from a 32-year-old woman who had developed Type-1 diabetes at the age of ten, might herald the daystill far in the futurewhen scientists replace dysfunctional cells with healthy cells identical to the patient's own but grown in the lab.

The work was led by Dieter Egli of the New York Stem Cell Foundation (NYSCF) and was published Monday in Nature.

"This is a really important step forward in our quest to develop healthy, patient-specific stem cells that can be used to replace cells that are diseased or dead," said Susan Solomon, chief executive officer of NYSCF, which she co-founded in 2005 partly to search for a cure for her son's diabetes.

Stem cells could one day be used to treat not only diabetes but also other diseases, such as Parkinson's and Alzheimer's.

Embryonic Stem Cells Morph Into Beta Cells

In Type 1 diabetes, the body loses its ability to produce insulin when insulin-producing beta cells in the pancreas become damaged. Ideally this problem could be corrected with replacement therapy, using stem cells to create beta cells the body would recognize as its own because they contain the patient's own genome. This is the holy grail of personalized medicine.

To create a patient-specific line of embryonic stem cells, Egli and his colleagues used a technique known as somatic cell nuclear transfer. They took skin cells from the female patient, removed the nucleus from one cell and then inserted it into a donor egg cellan oocytefrom which the nucleus had been removed.

They stimulated the egg to grow until it became a blastocyst, a hundred-cell embryo in which some cells are "pluripotent," or capable of turning into any type of cell in the body. The researchers then directed a few of those embryonic stem cells to become beta cells. To their delight, the beta cells in the lab produced insulin, just as they would have in the body.

This research builds on work done last year in which scientists from the Oregon Health and Science University used the somatic cell nuclear transfer technique with skin cells from a fetus. It also advances previous work done by Egli and his colleagues in 2011, in which they created embryonic stem cell lines with an extra set of chromosomes. (The new stem cells, and the ones from Oregon, have the normal number of chromosomes.)

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Scientists Create Personalized Stem Cells, Raising Hopes for Diabetes Cure

PUBLIC RELEASE DATE:

28-Apr-2014

Contact: David McKeon dmckeon@nyscf.org 212-365-7440 New York Stem Cell Foundation

NEW YORK, NY (April 28, 2014) Using somatic cell nuclear transfer, a team of scientists led by Dr. Dieter Egli at the New York Stem Cell Foundation (NYSCF) Research Institute and Dr. Mark Sauer at Columbia University Medical Center has created the first disease-specific embryonic stem cell line with two sets of chromosomes.

As reported today in Nature, the scientists derived embryonic stem cells by adding the nuclei of adult skin cells to unfertilized donor oocytes using a process called somatic cell nuclear transfer (SCNT). Embryonic stem cells were created from one adult donor with type 1 diabetes and a healthy control. In 2011, the team reported creating the first embryonic cell line from human skin using nuclear transfer when they made stem cells and insulin-producing beta cells from patients with type 1 diabetes. However, those stem cells were triploid, meaning they had three sets of chromosomes, and therefore could not be used for new therapies.

The investigators overcame the final hurdle in making personalized stem cells that can be used to develop personalized cell therapies. They demonstrated the ability to make a patient-specific embryonic stem cell line that has two sets of chromosomes (a diploid state), the normal number in human cells. Reports from 2013 showed the ability to reprogram fetal fibroblasts using SCNT; however, this latest work demonstrates the first successful derivation by SCNT of diploid pluripotent stem cells from adult and neonatal somatic cells.

"From the start, the goal of this work has been to make patient-specific stem cells from an adult human subject with type 1 diabetes that can give rise to the cells lost in the disease," said Dr. Egli, the NYSCF scientist who led the research and conducted many of the experiments. "By reprograming cells to a pluripotent state and making beta cells, we are now one step closer to being able to treat diabetic patients with their own insulin-producing cells."

"I am thrilled to say we have accomplished our goal of creating patient-specific stem cells from diabetic patients using somatic cell nuclear transfer," said Susan L. Solomon, CEO and co-founder of NYSCF. "I became involved with medical research when my son was diagnosed with type 1 diabetes, and seeing today's results gives me hope that we will one day have a cure for this debilitating disease. The NYSCF laboratory is one of the few places in the world that pursues all types of stem cell research. Even though many people questioned the necessity of continuing our SCNT work, we felt it was critical to advance all types of stem-cell research in pursuit of cures. We don't have a favorite cell type, and we don't yet know what kind of cell is going to be best for putting back into patients to treat their disease."

The research is the culmination of an effort begun in 2006 to make patient-specific embryonic stem cell lines from patients with type 1 diabetes. Ms. Solomon opened NYSCF's privately funded laboratory on March 1, 2006, to facilitate the creation of type 1 diabetes patient-specific embryonic stem cells using SCNT. Initially, the stem cell experiments were done at Harvard and the skin biopsies from type 1 diabetic patients at Columbia; however, isolation of the cell nuclei from these skin biopsies could not be conducted in the federally funded laboratories at Columbia, necessitating a safe-haven laboratory to complete the research. NYSCF initially established its lab, now the largest independent stem cell laboratory in the nation, to serve as the site for this research.

In 2008, all of the research was moved to the NYSCF laboratory when the Harvard scientists determined they could no longer move forward, as restrictions in Massachusetts prevented their obtaining oocytes. Dr. Egli left Harvard University and joined NYSCF; at the same time, NYSCF forged a collaboration with Dr. Sauer who designed a unique egg-donor program that allowed the scientists to obtain oocytes for the research.

Read more from the original source:
First disease-specific human embryonic stem cell line by nuclear transfer

Bjarki Johannesson, NYSCF

This colony of embryonic stem cells, created from a type 1 diabetes patient, is one of the first to be cloned from an adult human.

Two research groups have independently produced human embryonic stem-cell lines from embryos cloned from adult cells. Their success could reinvigorate efforts to use such cells to make patient-specific replacement tissues for degenerative diseases, for example to replace pancreatic cells in patients with type 1 diabetes. But further studies will be needed before such cells can be tested as therapies.

The first stem-cell lines from cloned human embryos were reported in May last year by a team led by reproductive biology specialist Shoukhrat Mitalipov of the Oregon Health & Science University in Beaverton (see 'Human stem cells created by cloning'). Those cells carried genomes taken from fetal cells or from cells of an eight-month-old baby1, and it was unclear whether this would be possible using cells from older individuals. (Errors were found in Mitalipov's paper, but were not deemed to affect the validity of its results.)

Now two teams have independently announced success. On 17 April, researchers led by Young Gie Chung and Dong Ryul Lee at the CHA University in Seoul reported inCell Stem Cell that they had cloned embryonic stem-cell (ES cell) lines made using nuclei from two healthy men, aged 35 and 752. And in a paper published on Nature's website today, a team led by regenerative medicine specialist Dieter Egli at the New York Stem Cell Foundation Research Institute describes ES cells derived from a cloned embryo containing the DNA from a 32-year-old woman with type 1 diabetes. The researchers also succeeded in differentiating these ES cells into insulin-producing cells3.

To produce the cloned embryos, all three groups used an optimized version of the laboratory technique called somatic-cell nuclear transfer (SCNT), where the nucleus from a patient's cell is placed into an unfertilized human egg which has been stripped of its own nucleus. This reprograms the cell into an embryonic state. SCNT was the technique used to create the first mammal cloned from an adult cell, Dolly the sheep, in 1996.

The studies show that the technique works for adult cells and in multiple labs, marking a major step. It's important for several reasons, says Robin Lovell-Badge, a stem-cell biologist at the MRC National Institute for Medical Research in London.

At present, studies to test potential cell therapies derived from ES cells are more likely to gain regulatory approval than those testing therapies derived from induced pluripotent stem (iPS) cells, which are made by adding genes to adult cells to reprogram them to an embryonic-like state. Compared with iPS cells, ES cells are less variable, says Lovell-Badge. Therapies for spinal-cord injury and eye disease using non-cloned ES cells have already been tested in human trials. But while many ES cell lines have been made using embryos left over from fertility treatments, stem cells made from cloned adult cells are genetically matched to patients and so are at less risk of being rejected when transplanted.

Lovell-Badge says cloned embryos could also be useful in other ways, in particular to improve techniques for reprogramming adult cells and to study cell types unique to early-stage embryos, such as those that go on to form the placenta.

Few, however, expect a huge influx of researchers making stem cells from cloned human embryos. The technique is expensive, technically difficult and ethically fraught. It creates an embryo only for the purpose of harvesting its cells. Obtaining human eggs also requires regulatory clearance to perform an invasive procedure on healthy young women, who are paid for their time and discomfort.

The rest is here:
Stem cells made by cloning adult humans

The new approach does not use fertilized embryos to obtain stem cells, a technique that raises major ethical issues

STEM CELLS UP CLOSE. This handout picture, released from Japan's Kyoto University Center for iPS Cell Research and Application (CiRA) on January 23, 2013 shows part of the renal tubule cells (red part) which were differentiated from human stem cells at the CiRA in Kyoto. Kyoto University/AFP

WASHINGTON, USA For the first time, US researchers have cloned embryonic stem cells from adult cells, a breakthrough on the path towards helping doctors treat a host of diseases.

The embryonic stem cells which were created by fusing an adult skin cell with an egg cell that had been stripped of genetic material were genetically identical to the donors.

The hope is that cloned embryonic stem cells, which are capable of transforming into any other type of cell in the body, could be used in patient-specific regenerative therapy to repair or replace an individual's organs damaged by diseases including cancer, heart disease and Alzheimer's disease.

The team of researchers, led by Robert Lanza, of the Massachusetts-based company Advanced Cell Technology, used a technique that had succeeded last year with infant skin cells.

But Lanza's team, funded in part by the South Korean government, used cells from a 35-year-old man and a 75-year-old man.

This is a significant step forward, the researchers wrote in the study published Thursday, April 17, in the journal Cell Stem Cell.

"For many cell types, reprogramming is more difficult for adult cells than for fetal/infant cells, presumably at least in part because (they are) ... further removed from the pluripotent state" in which the cells can develop into different types, the study said.

Yet adults are more likely than infants to need regenerative therapy, the authors wrote, noting that "the incidence of many diseases that could be treated with pluripotent cell derivatives increases with age."

See more here:
US scientists make embryonic stem cells from adult skin

Health

After years of failed attempts, researchers have finally generated stem cells from adults using the same cloning technique that produced Dolly the sheep in 1996.

A previous claim that Korean investigators had succeeded in the feat turned out to be fraudulent. Then last year, a group at Oregon Health & Science University generated stem cells using the Dolly technique, but with cells from fetuses and infants.

MORE: Stem-Cell Research: The Quest Resumes

In this case, cells from a 35-year-old man and a 75-year-old man were used to generate two separate lines of stem cells. The process, known as nuclear transfer, involves taking the DNA from a donor and inserting it into an egg that has been stripped of its DNA. The resulting hybrid is stimulated to fuse and start dividing; after a few days the embryo creates a lining of stem cells that are destined to develop into all of the cells and tissues in the human body. Researchers extract these cells and grow them in the lab, where they are treated with the appropriate growth factors and other agents to develop into specific types of cells, like neurons, muscle, or insulin-producing cells.

Reporting in the journal Cell Stem Cell, Dr. Robert Lanza, chief scientific officer at biotechnology company Advanced Cell Technology, and his colleagues found that tweaking the Oregon teams process was the key to success with reprogramming the older cells. Like the earlier team, Lanzas group used caffeine to prevent the fused egg from dividing prematurely. Rather than leaving the egg with its newly introduced DNA for 30 minutes before activating the dividing stage, they let the eggs rest for about two hours. This gave the DNA enough time to acclimate to its new environment and interact with the eggs development factors, which erased each of the donor cells existing history and reprogrammed it to act like a brand new cell in an embryo.

VIDEO: Breakthrough in Cloning Human Stem Cells: Explainer

The team, which included an international group of stem cell scientists, used 77 eggs from four different donors. They tested their new method by waiting for 30 minutes before activating 38 of the resulting embryos, and waiting two hours before triggering 39 of them. None of the 38 developed into the next stage, while two of the embryos getting extended time did. There is a massive molecular change occurring. You are taking a fully differentiated cell, and you need to have the egg do its magic, says Lanza. You need to extend the reprogramming time before you can force the cell to divide.

While a 5% efficiency may not seem laudable, Lanza says that its not so bad given that the stem cells appear to have had their genetic history completely erased and returned to that of a blank slate. This procedure works well, and works with adult cells, says Lanza.

The results also teach stem cell scientists some important lessons. First, that the nuclear transfer method that the Oregon team used is valid, and that with some changes it can be replicated using older adult cells. It looks like the protocols we described are real, they are universal, they work in different hands, in different labs and with different cells, says Shoukhrat Mitalopov, director of the center for embryonic cell and gene therapy at Oregon Health & Science University, and lead investigator of that study.

Read more:
Researchers Clone Cells From Two Adult Men

14/04/2014 - 13:40:33Back to World Home

Red blood cells grown in a laboratory are to be tested in patients for the first time by pioneering scientists.

The first volunteers are expected to be treated by late 2016. If successful, the trial could pave the way to the wide-scale use of artificial blood derived from stem cells.

Blood cells freshly made in the laboratory are likely to have a longer life span than those taken from donors, which typically last no more than 120 days.

They would also be free from infectious agents such as viruses or the rogue prion proteins that cause Creuzfeldt-Jakob Disease (CJD).

Professor Marc Turner, medical director at the Scottish National Blood Transfusion Service (SNBTS), who is leading the 5m project at the University of Edinburgh, said: Producing a cellular therapy which is of the scale, quality and safety required for human clinical trials is a very significant challenge. But if we can achieve success with this first-in-man clinical study it will be an important step forward to enable populations all over the world to benefit from blood transfusions.

These developments will also provide information of value to other researchers working on the development of cellular therapies.

The pilot study will involve no more than about three patients, who may be healthy volunteers or individuals suffering from a red blood cell disorder such as thalassaemia.

They will receive a small, five millilitre dose of laboratory-made blood to see how it behaves and survives in their bodies.

The blood cells will be created from ordinary donated skin cells called fibroblasts which are genetically reprogrammed into a stem cell-like state.

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Scientists to test artificial blood in humans

The first volunteers are expected to be treated by late 2016. If successful, the trial could pave the way to the wide-scale use of artificial blood derived from stem cells.

Blood cells freshly made in the laboratory are likely to have a longer life span than those taken from donors, which typically last no more than 120 days.

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They would also be free from infectious agents such as viruses or the rogue prion proteins that cause Creuzfeldt-Jakob Disease (CJD).

Professor Marc Turner, medical director at the Scottish National Blood Transfusion Service (SNBTS), who is leading the 5 million project at the University of Edinburgh, said: "Producing a cellular therapy which is of the scale, quality and safety required for human clinical trials is a very significant challenge.

"But if we can achieve success with this first-in-man clinical study it will be an important step forward to enable populations all over the world to benefit from blood transfusions.

"These developments will also provide information of value to other researchers working on the development of cellular therapies."

The pilot study will involve no more than about three patients, who may be healthy volunteers or individuals suffering from a red blood cell disorder such as thalassaemia.

They will receive a small, five millilitre dose of laboratory-made blood to see how it behaves and survives in their bodies.

The blood cells will be created from ordinary donated skin cells called fibroblasts which are genetically reprogrammed into a stem cell-like state.

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In the blood: Scottish scientists pioneer lab-grown cells

Lexington, MA (PRWEB) March 24, 2014

Today, the FSH Society, a Massachusetts based non-profit that is a world leader in combating facioscapulohumeral dystrophy (FSHD), announced that it has awarded six grants totaling more $609,525 to new research projects. Through these studies, the FSH Societys fellowship program aims to gain insights and achieve significant milestones into the research of FSHD, one of the most prevalent types of muscular dystrophy.

A degenerative muscle disease, FSHD causes progressive weakness, usually starting with the face, shoulder and arms, but can affect almost any skeletal muscle. FSHD affects approximately 500,000 people worldwide and between one and two percent of the population carries a genetic trait that places future generations at risk of the disease. Currently, there is no cure or effective treatment.

Research grants most recently awarded by the FSH Society include: 1.Investigating effects of PARP1 inhibitors in DUX4 expression ($89,267) Yi-Wen Chen, D.V.M., Ph.D. George Washington University and Childrens National Medical Center (Washington, D.C.) A mysterious protein called DUX4 is believed to cause FSHD. The findings of the study will provide insights of the involvement of PARP1, a promoter of the DUX4 gene, in FSHD, and will have a direct impact on developing therapeutics for FSHD.

2.Gene surgery using TALEN technology: a therapy for FSHD ($117,500) Julie Dumonceaux, Ph.D. Institut de Myologie, University of Paris, U974 (Inserm, Paris, France) The approach proposed in this study unlike other therapeutic strategies under investigation for FSHD does not require repeated long-term administration of treatment. The benefits of this as a clinical therapy include lower cost and reduced toxicological and immunological risk. Moreover, this approach would be useful for all FSHD cases, regardless of the precise mutation or contraction involved.

3.Protein chemistry and protein-protein interactions of DUX4 ($70,000) Jocelyn Eidahl, Ph.D. The Research Institute at Nationwide Childrens Hospital (Columbus, OH) DUX4 has been identified as potential cause for FSHD, but the mechanisms by which DUX4 contributes to FSHD pathologies is unclear. The studys hypothesis is that the DUX4 transcription factor is involved in protein-protein interactions that influence its ability to induce toxicity in muscle cells and ultimately contribute to FSHD. The study examines the functional significance of protein-protein interactions of DUX4 that are critical for DUX4 toxicity.

4.Exploiting genome editing technology to modify and regulate the FSHD disease locus ($125,000) Supported in part by a generous gift from the FSHD Canada Foundation. Michael Kyba, Ph.D. Lillehei Heart Institute, University of Minnesota (Minneapolis, MN) Recent discoveries of DNA-binding factors have opened up tremendous new possibilities in genome editing. Through the grant, this study will take advantage of and leverage an existing research program in genome editing of FSHD iPS cells, and will provide the field with valuable new tools to study the pathogenesis of FSHD, and to develop cell therapies based on corrected, isogenic, iPS cells.

5.Microdialysis for the study of inflammatory features in FSHD ($70,000) Giorgio Tasca, M.D. Institute of Neurology, Catholic University School of Medicine (Rome, Italy) The study will implement a technique that has never been applied to the study of skeletal muscle and provide a better understanding of the role of the inflammatory process in the disease, the identification of biomarkers of disease activity at single muscle level and the acquisition of information useful for the development of a targeted anti-inflammatory therapy. In the future, the new technique could be used for molecular monitoring and eventually drug administration in neuromuscular disorders.

6.Dynamic mapping of perturbed signaling underlying FSHD ($137,798) Peter S. Zammit, Ph.D. Kings College London (London, England) Results gained through the study will identify methods that could help restore muscle regeneration in FSHD, reversing muscle weakness and wasting. The researchs ultimate aim is to gain knowledge on FSHD myogenesis and inform the design of therapies for FSHD.

These new studies represent a crucial step in the ongoing development of FSHD treatments and cures, said Daniel Perez, President & CEO of the FSH Society. We are thrilled to award the grants to such innovative research endeavors, which bring us closer to finding more effective treatments and medical breakthroughs for FSHD.

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The FSH Society Issues Six Research Grants to Propel Understanding and Treatment of FSHD

Mouse cells exposed to an acidic environment turned into embryonic-like "STAP" cells. These were used to generate an entire fetus.

A coauthor of a disputed study on a new way generating stem cells through exposure to acid and other stresses has asked for its retraction, it was reported Monday.

Teruhiko Wakayama asked for retraction of two papers describing so-called STAP cells, according to the Yomiuri Shimbun. The papers had been published in the Jan. 30 edition of the journal Nature. Other news outlets, including the Wall Street Journal and the Boston Globe, quickly followed up with the call for retraction.

The original announcement gained worldwide attention because it promised an easy way to generate pluripotent stem cells, which act like embryonic stem cells. Simply immersing cells in an acid bath or squeezing them was enough to reprogram them to the embryonic-like state, the scientists reported. The acronym STAP stands for stimulus-triggered acquisition of pluripotency.

However, researchers attempting to replicate the experiment, including those at the Salk Institute and The Scripps Research Institute in La Jolla, have so far reported failure. And errors in the papers, including duplication of images, have caused scientists to question the findings.

The first author of both papers is Haruko Obokata, 30, of the Riken Center for Developmental Biology in Japan. She was hailed as a scientific prodigy after the research was published. Another coauthor, Charles Vacanti, chairman of the Anesthesiology department at Brigham and Womens Hospital in Boston, had previously said the errors were caused by overwork and didn't affect the results.

As recently as Feb. 27, Wakayama said scientists should give replication efforts a year before passing judgment.

But on Monday, Wakayama said the irregularities render the findings questionable.

"Wakayama said images that show pluripotency of STAP cells look almost identical to those used in Obokatas doctoral thesis about pluripotent stem cells that exist in human body," the Yomiuri Shimbun reported.

Wakayama is probably acting out of a sense of duty, said Jeanne Loring, a stem cell scientist at The Scripps Research Institute.

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STAP cells paper coauthor asks for retraction

PUBLIC RELEASE DATE:

9-Mar-2014

Contact: Henry Rummins h.rummins@ucl.ac.uk 44-207-679-9063 University College London

Japanese pharmaceutical company Takeda will work with University College London (UCL) to drive research into tackling muscle disorders, in particular muscular dystrophy.

The research which is being conducted by the research group of Dr Francesco Saverio Tedesco is being supported through funding of $250,000 from the company's New Frontier Sciences group. Takeda's NFS aims to support innovative, cutting-edge research which could eventually lead to drug discovery and development.

Dr Tedesco's team will focus on the study of muscular regeneration and the potential for stem cell therapies to treat muscular dystrophy, in particular induced pluripotent (iPS) stem cells.

The team is also investigating the potential for treating muscular dystrophy through developing novel gene and cell therapy strategies using artificial human chromosomes and novel biomaterials.

Using this approach, Dr Tedesco hopes to overcome a number of current limitations to developing effective treatments for muscular dystrophies. It is hoped that through the use of these modified stem cells, large quantities of progenitor cells could be produced to be transplanted into a patient's muscle following genetic correction or to be used for drug development platforms.

Importantly, the team will attempt to produce these cells which can be applied more easily in a clinical context, in order to reduce the hurdles that might limit their possible future use in clinical studies.

Through previous work using a mouse model of Duchenne muscular dystrophy, the team has already demonstrated the potential of pre-clinical gene replacement therapy using an artificial human chromosome.

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Takeda and UCL to work together to tackle muscle disorders

Somerset, NJ (PRWEB) March 06, 2014

Catalent Pharma Solutions, the global leader in advanced delivery technologies and development solutions for drug, biologic and consumer health products, today announced an agreement with the Center for iPS Cell Research and Application (CiRA) at Kyoto University in Japan to make a major advancement toward one of the first regenerative human therapies with induced pluripotent stem (iPS) cells applicable to humans. Under this agreement, Catalent manufactures an anti-CORIN monoclonal antibody using its proprietary GPEx cell line expression technology for a planned clinical research project to develop an iPS cell-based transplant therapy for Parkinsons disease at CiRA, which is directed by Professor Doctor Shinya Yamanaka, the joint winner of the Nobel Prize in Physiology or Medicine in 2012 for the discovery that mature cells can be reprogrammed to become pluripotent.

The anti-CORIN monoclonal antibody was discovered and developed through collaborative research between CiRA and KAN Research Institute, Inc., a research subsidiary of a major Japanese pharmaceutical company, Eisai Co., Ltd-(http://www.kan-research.co.jp/english/index.html). Catalent has already engineered cell lines producing the anti-CORIN monoclonal antibody for CiRA using their GPEx technology, and the antibody has been shown to be useful for sorting CORIN-expressing cells in in vitro studies at CiRA. Under the agreement, Catalent will conduct further clonal selection and manufacturing of the monoclonal antibody under a properly conditioned environment for CiRA, which will use the antibody to select dopaminergic neurons derived from iPS cells and plans to transplant the selected cells into patients in a possible clinical research program upon receipt of regulatory approval. Catalent will also support CiRA, with formulation, production, and sterile fill/finish of the monoclonal antibody, aspects of the project that could not be handled within academia.

It is a great honor to work with a team led by world renowned Professor Doctor Jun Takahashi, commented Shingo Nakamura, Catalents Director of Biologics, Japan. We are very excited to help accelerate the development of a unique regenerative therapy using our GPEx technology and look forward to working with CiRA to bring better treatments to market faster.

Jonathan Arnold, Vice President and General Manager of Catalent Biologics, added, We are witnessing an increased demand for biologics in the Asia Pacific market. Our GPEx technology, our expertise, and access to Antibody Drug Conjugates, combined with our investment in state-of-the art manufacturing facilities, mean that we are ideally placed to act as a partner to CiRA in this exciting project.

Catalents GPEx technology produces high-yielding, stable mammalian cell lines and has been successfully applied in the manufacture of more than 500 different recombinant proteins, over 30 of which are now undergoing clinical trials or being supplied commercially. Antibiotic selection and traditional gene amplification are not required when using GPEx technology, resulting in shorter clonal cell line development timelines.

About Catalent Catalent Pharma Solutions is the leading global provider of advanced drug delivery technologies and development solutions for drugs, biologics and consumer health products. With over 80 years serving the industry, Catalent has proven expertise in bringing more customer products to market faster, enhancing product performance and ensuring reliable clinical and commercial product supply. Catalent employs approximately 8,500 people, including over 1,000 scientists, at nearly 30 facilities across 5 continents and in fiscal 2013 generated more than $1.8 billion in annual revenue. Catalent is headquartered in Somerset, N.J. For more information, visit http://www.catalent.com.

More products. Better treatments. Reliably supplied.

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Catalent Announces Agreement for One of the First Regenerative Therapies to Employ iPS Cells in Humans with CiRA ...

Doubts keep growing about the stunning discovery that super stem cells could be created merely by placing white blood cells from young mice in acid or otherwise stressing them, says Paul Knoepfler, a stem cell researcher at UC Davis.

Among other inconsistencies, Knoepfler referred to several unexplained anomalies in images of these STAP cells in two papers, published by the prestigious journal Nature on Jan. 29. One image appears to suggest signs that virtually all cells treated with an acid bath were being reprogrammed, a result that would be extraordinary. Stem cell reprogramming to date has been inefficient, with a low percentage of treated cells being reprogrammed.

"The more I look at these two STAP papers, the more concerned I get ... The bottom line for me now is that some level a part of me still clings to a tiny and receding hope this has all been overblown due to simple misunderstandings, but that seems increasingly unlikely," Knoepfler wrote Sunday on his blog, IPS Cell.

This undated image made available by the journal Nature shows a mouse embryo formed with specially-treated cells from a newborn mouse that had been transformed into stem cells. Researchers in Boston and Japan say they created stem cells from various tissues of newborn mice. If the same technique works for humans, it may provide a new way to grow tissue for treating illnesses like diabetes and Parkinson's disease. The report was published online on Wednesday, Jan. 29, 2014 in the journal Nature. (AP Photo/RIKEN Center for Developmental Biology, Haruko Obokata)

Nature is conducting its own investigation, Knoepfler noted. But in addition, the journal should release "unmodified, original versions" of the images and data in the papers, Knoepfler wrote.

The images contained "minor errors" that didn't change the basic findings, said Charles Vacanti, a Harvard University professor who is part of the scientific team reporting the discovery, according to a Feb. 22 article in a Japanese newspaper, the Asahi Shimbun.

Controversy is normal for any major scientific advance. Skeptics must be converted, and the only way to do that is to show the data. The 1997 announcement of the first mammalian clone, Dolly the sheep, was greeted with considerable doubt because it was believed that genetic imprinting made such cloning impossible. But others were eventually able to confirm the finding.

In this case, doubters say such an apparently easy method of reprogramming cells would generate pluripotent stem cells far too easily, because stress is common in animals. Such stem cells are known to cause tumors, so evolution should have selected against such a response.

Nature's own role has been criticized. The journal was taken to task for its handling of online journalism Feb. 20 by another stem cell blogger, Alexey Bersenev. He chided Nature for not linking to sources.

"In scientific journalism, every claim must be linked to appropriate original source," Berseney wrote. "Nature consistently refuses to acknowledge bloggers, online discussions and other web resources with valid credible information. This is not acceptable for sci journalism."

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STAP stem cell doubts keep proliferating

La Jolla, CAA study led by researchers at the Salk Institute for Biological Studies, has catapulted the field of regenerative medicine significantly forward, proving in principle that a human genetic disease can be cured using a combination of gene therapy and induced pluripotent stem (iPS) cell technology. The study, published in the May 31, 2009 early online edition of Nature, is a major milestone on the path from the laboratory to the clinic.

"It's been ten years since human stem cells were first cultured in a Petri dish," says the study's leader Juan-Carlos Izpisa Belmonte, Ph.D., a professor in the Gene Expression Laboratory and director of the Center of Regenerative Medicine in Barcelona (CMRB), Spain. "The hope in the field has always been that we'll be able to correct a disease genetically and then make iPS cells that differentiate into the type of tissue where the disease is manifested and bring it to clinic."

Genetically-corrected fibroblasts from Fanconi anemia patients (shown in green at the top) are reprogrammed to generate induced pluripotent stem cells, which, in turn, can be differentiated into disease-free hematopoietic progenitors, capable of producing blood cells in vitro (bottom: Erythroid colonies.)

Image: Courtesy of Dr. Juan-Carlos Belmonte, Salk Institute for Biological Studies.

Although several studies have demonstrated the efficacy of the approach in mice, its feasibility in humans had not been established. The Salk study offers the first proof that this technology can work in human cells.

Belmonte's team, working with Salk colleague Inder Verma, Ph.D., a professor in the Laboratory of Genetics, and colleagues at the CMRB, and the CIEMAT in Madrid, Spain, decided to focus on Fanconi anemia (FA), a genetic disorder responsible for a series of hematological abnormalities that impair the body's ability to fight infection, deliver oxygen, and clot blood. Caused by mutations in one of 13 Fanconi anemia (FA) genes, the disease often leads to bone marrow failure, leukemia, and other cancers. Even after receiving bone marrow transplants to correct the hematological problems, patients remain at high risk of developing cancer and other serious health conditions.

After taking hair or skin cells from patients with Fanconi anemia, the investigators corrected the defective gene in the patients' cells using gene therapy techniques pioneered in Verma's laboratory. They then successfully reprogrammed the repaired cells into induced pluripotent stem (iPS) cells using a combination of transcription factors, OCT4, SOX2, KLF4 and cMYC. The resulting FA-iPS cells were indistinguishable from human embryonic stem cells and iPS cells generated from healthy donors.

Since bone marrow failure as a result of the progressive decline in the numbers of functional hematopoietic stem cells is the most prominent feature of Fanconi anemia, the researchers then tested whether patient-specific iPS cells could be used as a source for transplantable hematopoietic stem cells. They found that FA-iPS cells readily differentiated into hematopoietic progenitor cells primed to differentiate into healthy blood cells.

"We haven't cured a human being, but we have cured a cell," Belmonte explains. "In theory we could transplant it into a human and cure the disease."

Although hurdles still loom before that theory can become practice-in particular, preventing the reprogrammed cells from inducing tumors-in coming months Belmonte and Verma will be exploring ways to overcome that and other obstacles. In April 2009, they received a $6.6 million from the California Institute Regenerative Medicine (CIRM) to pursue research aimed at translating basic science into clinical cures.

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Genetic Re-disposition: Combined stem cell-gene therapy ...

20 hours ago This image shows iPS cells (green) generated using histone variants TH2A and TH2B and two Yamanaka factors (Oct3/4 and Klf4). Credit: RIKEN

One major challenge in stem cell research has been to reprogram differentiated cells to a totipotent state. Researchers from RIKEN in Japan have identified a duo of histone proteins that dramatically enhance the generation of induced pluripotent stem cells (iPS cells) and may be the key to generating induced totipotent stem cells.

Differentiated cells can be coaxed into returning to a stem-like pluripotent state either by artificially inducing the expression of four factors called the Yamanaka factors, or as recently shown by shocking them with sublethal stress, such as low pH or pressure. However, attempts to create totipotent stem cells capable of giving rise to a fully formed organism, from differentiated cells, have failed.

The study, published today in the journal Cell Stem Cell and led by Dr. Shunsuke Ishii from RIKEN, sought to identify the molecule in the mammalian oocyte that induces the complete reprograming of the genome leading to the generation of totipotent embryonic stem cells. This is the mechanism underlying normal fertilization, as well as the cloning technique called Somatic-Cell Nuclear Transfer (SCNT).

SCNT has been used successfully to clone various species of mammals, but the technique has serious limitations and its use on human cells has been controversial for ethical reasons.

Ishii and his team chose to focus on two histone variants named TH2A and TH2B, known to be specific to the testes where they bind tightly to DNA and affect gene expression.

The study demonstrates that, when added to the Yamanaka cocktail to reprogram mouse fibroblasts, the duo TH2A/TH2B increases the efficiency of iPSC cell generation about twentyfold and the speed of the process two- to threefold. And TH2A and TH2B function as substitutes for two of the Yamanaka factors (Sox2 and c-Myc).

By creating knockout mice lacking both proteins, the researchers show that TH2A and TH2B function as a pair, are highly expressed in oocytes and fertilized eggs and are needed for the development of the embryo after fertilization, although their levels decrease as the embryo grows.

In the early embryo, TH2A and TH2B bind to DNA and induce an open chromatin structure in the paternal genome, thereby contributing to its activation after fertilization.

These results indicate that TH2A/TH2B might induce reprogramming by regulating a different set of genes than the Yamanaka factors, and that these genes are involved in the generation of totipotent cells in oocyte-based reprogramming as seen in SCNT.

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Histones may hold the key to the generation of totipotent stem cells

Mouse cells exposed to an acidic environment turned into embryonic-like "STAP" cells. These were used to generate an entire fetus.

A simple lab treatment can turn ordinary cells from mice into a new kind of stem cell, according to a surprising study that hints at a new way to grow tissue for treating illnesses like diabetes and Parkinsons disease.

Researchers in Boston and Japan exposed spleen cells from newborn mice to an acidic environment. In lab tests, that made the cells act like embryonic stem cells, showing enough versatility to produce the tissues of a mouse embryo, for example.

Cells from skin, muscle, fat and other tissue of newborn mice went through the same change, which could be triggered by exposing cells to any of a variety of stressful situations, researchers said.

Its very simple to do. I think you could do this actually in a college lab, said Dr. Charles Vacanti of Brigham and Womens Hospital in Boston, an author of two papers published online Wednesday by the journal Nature. They can be found here and here.

If it works in humans, the method could improve upon an existing method of generating artificial embryonic stem cells, called induced pluripotent stem cells. These IPS cells can be made from patients, then turned into the needed cells, reducing the possibility of transplant rejection. Pluripotent is a term for cells that act like embryonic stem cells, which can turn into nearly any tissue of the body, except for placental tissues.

In San Diego, scientists led by The Scripps Research Institutes Jeanne Loring propose to treat Parkinsons disease patients with brain cells generated from their own IPS cells. Because these cells arent taken from human embryos, they dont raise the ethical concerns some have with using embryonic stem cells.

However induced pluripotent stem cells are made by reprogramming ordinary cells with added genes or chemicals, which raises concerns about safety. The new method, in contrast, causes the cell to change its own behavior after researchers have applied an external stress. The actual DNA sequence is unaltered, creating a change that is epigenetic, or taking place outside the genome. Researchers dubbed the new cells STAP cells, for stimulus-triggered acquisition of pluripotency.

This is part of a shift in our view of pluripotency, Loring said by email. Eight years ago we thought that cells were stable -- whatever they are, they stay that way. Now, were thinking in terms of how powerful epigenetics is -- that we can change cell fate without changing their DNA.

Loring said it will take years to apply the new method for human therapy.

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New stem cell may aid medicine

PARIS: Scientists on Wednesday reported a simple way to turn animal cells back to a youthful, neutral state, a feat hailed as a "game-changer" in the quest to grow transplant tissue in the lab.

The research, reported in the journal Nature, could be the third great advance in stem cells -- a futuristic field that aims to reverse Alzheimer's, cancer and other crippling or lethal diseases.

The latest breakthrough comes from Japan, as did its predecessor which earned its inventor a Nobel Prize.

The new approach, provided it overcomes safety hurdles, could smash cost and technical barriers in stem-cell research, said independent commentators.

"If it works in man, this could be the game-changer that ultimately makes a wide range of cell therapies available using the patient's own cells as starting material," said Chris Mason, a professor of regenerative medicine at University College London.

"The age of personalised medicine will have arrived."

Stem cells are primitive cells that, as they grow, differentiate into the various specialised cells that make up the different organs -- the brain, the heart, the kidney and so on.

The goal is to create stem cells in the lab and nudge them to grow into these differentiated cells, thus replenishing organs damaged by disease or accident.

One of the obstacles, though, is ensuring that these transplanted cells are not attacked as alien by the body's immune system.

To achieve that, the stem cells would have to carry the patient's own genetic code, to identify them as friendly.

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Stem cells in "revolutionary" boost

Jan. 13, 2014 Geneticists from Ohio, California and Japan joined forces in a quest to correct a faulty chromosome through cellular reprogramming. Their study, published online today in Nature, used stem cells to correct a defective "ring chromosome" with a normal chromosome. Such therapy has the promise to correct chromosome abnormalities that give rise to birth defects, mental disabilities and growth limitations.

"In the future, it may be possible to use this approach to take cells from a patient that has a defective chromosome with multiple missing or duplicated genes and rescue those cells by removing the defective chromosome and replacing it with a normal chromosome," said senior author Anthony Wynshaw-Boris, MD, PhD, James H. Jewell MD '34 Professor of Genetics and chair of Case Western Reserve School of Medicine Department of Genetics and Genome Sciences and University Hospitals Case Medical Center.

Wynshaw-Boris led this research while a professor in pediatrics, the Institute for Human Genetics and the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UC, San Francisco (UCSF) before joining the faculty at Case Western Reserve in June 2013.

Individuals with ring chromosomes may display a variety of birth defects, but nearly all persons with ring chromosomes at least display short stature due to problems with cell division. A normal chromosome is linear, with its ends protected, but with ring chromosomes, the two ends of the chromosome fuse together, forming a circle. This fusion can be associated with large terminal deletions, a process where portions of the chromosome or DNA sequences are missing. These deletions can result in disabling genetic disorders if the genes in the deletion are necessary for normal cellular functions.

The prospect for effective counter measures has evaded scientists -- until now. The international research team discovered the potential for substituting the malfunctioning ring chromosome with an appropriately functioning one during reprogramming of patient cells into induced pluripotent stem cells (iPSCs). iPSC reprogramming is a technique that was developed by Shinya Yamanaka, MD, PhD, a co-corresponding author on the Nature paper. Yamanaka is a senior investigator at the UCSF-affiliated Gladstone Institutes, a professor of anatomy at UCSF, and the director of the Center for iPS Cell Research and Application (CiRA) at the Institute for Integrated Cell-Material Sciences (iCeMS) in Kyoto University. He won the Nobel Prize in Medicine in 2012 for developing the reprogramming technique.

Marina Bershteyn, PhD, a postdoctoral fellow in the Wynshaw-Boris lab at UCSF, along with Yohei Hayashi, PhD, a postdoctoral fellow in the Yamanaka lab at the Gladstone Institutes, reprogrammed skin cells from three patients with abnormal brain development due to a rare disorder called Miller Dieker Syndrome, which results from large terminal deletions in one arm of chromosome 17. One patient had a ring chromosome 17 with the deletion and the other two patients had large terminal deletions in one of their chromosome 17, but not a ring. Additionally, each of these patients had one normal chromosome 17.

The researchers observed that, after reprogramming, the ring chromosome 17 that had the deletion vanished entirely and was replaced by a duplicated copy of the normal chromosome 17. However, the terminal deletions in the other two patients remained after reprogramming. To make sure this phenomenon was not unique to ring chromosome 17, they reprogrammed cells from two different patients that each had ring chromosomes 13. These reprogrammed cells also lost the ring chromosome, and contained a duplicated copy of the normal chromosome 13.

"It appears that ring chromosomes are lost during rapid and continuous cell divisions during reprogramming," said Yamanaka. "The duplication of the normal chromosome then corrects for that lost chromosome."

"Ring loss and duplication of whole chromosomes occur with a certain frequency in stem cells," explained Bershteyn. "When chromosome duplication compensates for the loss of the corresponding ring chromosome with a deletion, this provides a possible avenue to correct large-scale problems in a chromosome that have no chance of being corrected by any other means."

"It is likely that our findings apply to other ring chromosomes, since the loss of the ring chromosome occurred in cells reprogrammed from three different patients," said Hayashi.

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Study discovers chromosome therapy to correct severe chromosome defect

KYOTO A team of Japanese researchers has developed a new way to easily culture induced pluripotent stem cells that has a low risk of infection in transplant therapy, a British science journal reported.

The team, which includes Kyoto Universitys Center for iPS Cell Research and Application, can create a culture system that unlike the existing technique doesnt have to use animal ingredients, which are at risk of infection, the journal Scientific Reports said Wednesday.

The researchers said in the journal that the new culture system will be vital in speeding up efforts to apply iPS cells in regenerative medicine.

They found that using fragments of a protein called laminin-511, which can stick cells together, enables cells to be stable on culture dishes or plates. With the method, they have created a safer method for producing iPS cells using amino acids and vitamins instead of animal ingredients.

The conventional method for culturing iPS cells has been to graft them on cell culture dishes and used feeder cells or mouse cells and bovine serum-containing medium as nutrients.

But because there are risks to infections in using tissues and cells, which are created from iPS cells under the existing culture system, there is a need to conduct time-consuming safety tests, Scientific Reports said.

They discovered that human iPS cells developed based on this system can also transform into nerve cells that produce neurotransmitter dopamine, insulin-producing cells and blood cells.

The researchers hope the discovery will eventually lead to clinical applications for illnesses such as Parkinsons disease and diabetes.

The new culture system can also be applied to embryonic stem cells, the journal said.

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Team develops new way to culture iPS cells with reduced ...

WASHINGTON Every year, the editors of Science huddle together and pick an outstanding scientific achievement as the Breakthrough of the Year. This year's winner is:

CANCER IMMUNOTHERAPY: harnessing the immune system to battle tumors.

Scientists have thought for decades that such an approach to cancer therapy should be possible, but it has been incredibly difficult to make it work. Now many oncologists say we have turned a corner, because two different techniques are helping a subset of patients. One involves antibodies that release a brake on T cells, giving them the power to tackle tumors. Another involves genetically modifying an individual's T cells outside the body so that they are better able to target cancer, and then re-infusing them so they can do just that.

We are still at the beginning of this story and have a long way to go. Only a very small proportion of cancer patients have received these therapies, and many are not helped by them. Doctors and scientists still have a lot to learn about why the treatments do and do not work. But the results have been repeated at different centers and in different tumor types, giving doctors hope that immunotherapy for cancer may benefit more and more people in the future

The editors also singled out nine runners-up for special praise:

GENETIC MICROSURGERY

A year-old gene-editing technique called CRISPR touched off an explosion of research in 2013. It's short for "clustered regularly interspaced short palindromic repeats": repetitive stretches of DNA that bacteria have evolved to combat predatory viruses by slicing up the viral genomes. The "knife" is a protein called Cas9; in 2012, researchers showed they could use it as a scalpel to perform microsurgery on genes. This year the new technology became red hot, as more than a dozen teams wielded it to manipulate specific genes in mice, rats, bacteria, yeast, zebrafish, nematodes, fruit flies, plants and human cells, paving the way for understanding how these genes function and possibly harnessing them to improve health.

CLARITY BRAIN IMAGING

This year, researchers invented a new way of imaging the brain which many say will fundamentally change the way labs study the intricate organ. CLARITY, a method of rendering brain tissue transparent, removes the biggest obstacle to traditional brain imaging: the fatty, light-scattering molecules, called lipids, which form cellular membranes. By replacing lipids with single molecules of a clear gel, the technique renders brain tissue transparent while leaving all neurons, other brain cells and their organelles intact. This allows researchers to infiltrate the brain with labels for specific cell types, neurotransmitters, or proteins, wash them out, and image the brain again with different labels - a process they say could speed up by a hundredfold tasks such as counting all the neurons in a given brain region.

CLONING HUMAN STEM CELLS

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Science's top 10 breakthroughs of 2013

The most successful stem cell therapybone marrow transplanthas been around for more than 40 years. Johns Hopkins researchers played an integral role in establishing the methods for how bone marrow transplants are done, which you can read about in Human Stem Cells at Johns Hopkins: A Forty Year History. The latest developments in bone marrow transplants are Half-Matched Transplants, which may be helpful in treating more diseases than ever before. In The Promise of the Future, three Hopkins researchers who study blood diseases share their ideas about which technologies hold most promise for developing therapies.

Induced pluripotent stem cells, or iPS cells, are adult cells that are engineered to behave like stem cells and to regain the ability to differentiate into various cell types. Engineered Blood describes current research in generating blood cells that contain disease traits with Those Magic Scissors so we can learn more in the lab about diseases like sickle cell anemia.

Adult stem cells are being used in other applications as well. Stem Cells Enhance Healing tells of an undergraduate biomedical engineering team at Hopkins that has devised medical sutures containing stem cells which speed up healing when stitched in. And A New Path for Cardiac Stem Cells tells of how a patients own heart stem cells were used to repair his heart after a heart attack.

In the podcast What Anti-Depression Treatments Actually Target In The Brain, Hongjun Song reveals that current antidepressant therapies may have unknowingly been targeting stem cells all along.

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Stem Cell Research at Johns Hopkins Medicine: Stem Cell Therapy