Age Of Obama Stem Cell Research Continues With Government Funding

Stem cell research began with a goal of being able to cure persons based on their own unique genetic make-up and healing inefficiencies by using harvested cells. This week, a federal appeals court said the Obama led federal government can continue to fund research involving human embryonic stem cells. The 2-1 ruling overturned a trial judge's injunction in August 2010 that barred funding for the research. Since 1996 and the last Bush Administration, Congress has barred federal funds for research in which human embryos are destroyed.

There are enormous scientific challenges, but the most debated points of discussion, government intervention and personal doubt, come from intense ethical inclusions such as privacy, consent and at times the withdrawal of that consent to use embryos for example in this evolving treatment application.

One of President Barack Obama's first acts on science policy after taking office was to expand stem-cell research beyond limits set by President George W. Bush in August 2001. While Mr. Bush had limited research on embryonic stem cells to a small number of then-existing cell lines, Mr. Obama in March 2009 opened up federal funding to research using cells derived from embryos that were created by in-vitro fertilization for reproductive purposes and were no longer needed.

Supporters of the research say the stem cells, which can develop into any type of body tissue, could help treat ailments from diabetes to heart disease. There is a tremendous amount of preclinical testing that still needs to be done however, despite court ordered pauses in research or not.

Sen. Tom Harkin (D-Iowa), chairman of the Senate Health, Education, Labor and Pensions Committee, said:

"My hope is that the legal wrangling ends here. Because if the last few years have proven anything, it is that our fight to preserve funding for stem cell research,one of the most promising areas of medical research available today, must continue."

Treatments utilizing a variety of therapeutic options are potentially available, and seem to all be very promising. There is evidence supporting the therapeutic use of stem cells for acute and chronic diseases, but the adaptation of preclinical work to in-practice clinical application is a key challenge to the work as the results of several randomized clinical trials indicate.

Opponents question the morality of using cells derived from embryos in a process that destroys them, saying that amounts to taking a human life.

The court majority this week, and in an opinion by Judge Douglas H. Ginsburg, said that barring the funding would be a substantial blow to researchers.

Samuel B. Casey, a lawyer for the plaintiffs who oppose the research, said the ruling was a narrow one on the question of a preliminary injunction and didn't address most parts of the case:

"Scientists have pushed for federal funds to support embryonic stem-cell science because they believe it offers great promise in treating a host of diseases through tissue transplantation primarily. Privately funded research has continued, but federal money is the biggest source of funding for such projects. "

The National Institute of Health spent $1.4 billion on stem-cell research in 2010, including both embryonic and nonembryonic stem cells. The more-optimistic predictions about medical breakthroughs have failed to pan out so far, as scientists struggle to turn the basic research into practical therapies.

Dr. Francis S. Collins, director of the National Institutes of Health stated:

"This is a momentous day not only for science but for the hopes of thousands of patients and their families who are relying on N.I.H.-funded scientists to pursue life-saving discoveries and therapies that could come from stem cell research."

Read the 34 page reversal document in its entirety HERE.

Written by Sy Kraft
Copyright: Medical News Today

The Way Doctors Treat Patients With Cancer And Autoimmune Diseases Could Change Following New Discovery

Researchers in the Faculty of Medicine & Dentistry at the University of Alberta have made an important discovery that provides a new understanding of how our immune system "learns" not to attack our own body, and this could affect the way doctors treat patients with autoimmune diseases and cancer.

When patients undergo chemotherapy for cancer or as part of experimental therapies to treat autoimmune diseases such as diabetes and lupus, the treatment kills the patients' white blood cells. What can be done afterwards, is to give these patients blood stem cells through transplantation. Stem cells are taken from patients then injected back into them - with the theory being that the patients' immune system won't attack their own cells, and the stem cells can get to work healing their bodies.

But U of A medical researchers Govindarajan Thangavelu, Colin Anderson and their collaborators discovered that if a particular molecule is not working properly in T-cells, the body will attack itself. This is significant for stem-cell transplantation treatment because it means the immune systems of the patients could consider their own cells "foreign" and initiate an attack.

"So your own cells would be killing you," says Thangavelu, a PhD student specializing in immunology, who was the first author in the research study, which was recently published in the peer-reviewed Journal of Autoimmunity. "What we found is if this molecule is absent in T-cells, if the pathway isn't intact, it will cause severe autoimmunity to the subject's own body. In essence, subjects become allergic to their own cells."

Anderson, an associate professor with the Alberta Diabetes Institute and Principal Investigator added: "The ability of our immune system to attack dangerous microbes while not attacking our own cells or tissues is a delicate balance. Restarting the immune system after wiping it out in patients with autoimmune diseases or cancer requires re-establishing this appropriate balance. We discovered that a particular immune system molecule is critical to prevent the immune system from attacking our own cells or tissues when the immune system is restarted. If that molecule is missing, the immune system will wreak havoc on the body."

T-cells are supposed to protect people and animals from things invading their bodies. But this research demonstrates if these cells become unregulated because they are missing a molecule, it can lead to autoimmunity - particularly dangerous in scenarios where patients have lost white blood cells when they are being treated for autoimmune diseases or cancer.

Thangavelu has won awards for this research. He was invited to present his work at an international conference of immunology in Japan last year. He has also travelled to the United Kingdom to talk about his findings with the medical community.

This research was funded by: the Juvenile Diabetes Research Foundation, the Canadian Institutes of Health Research, Alberta Innovates-Health Solutions and the Alberta Diabetes Institute.

Source:
Raquel Maurier
University of Alberta Faculty of Medicine & Dentistry

Taking Blood From Fukushima Radiation Workers To Prepare For Future Stem Cell Transplants In Case They Are Exposed To High Doses Of Radiation

In Correspondence published Online First and an upcoming Lancet, Japanese experts suggest that blood products be taken from workers dealing with the ailing Fukushima Nuclear Facility-so that, should they accidently be exposed to high and health-damaging doses of radiation during the clean-up operation, they will be able to receive treatment by undergoing stem cell transplanation using their own cells (autologous transplant). The Correspondence authors are represented by Dr Shuichi Taniguchi, Toranomon Hospital, Tokyo, Japan, and Dr Tetsuya Tanimoto, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.

The authors say: "The danger of a future accidental radiation exposure is not passed, since there has been a series of serious aftershocks even [during] this April."

Generally, rapidly dividing cells, such as intestinal-tract cells, reproductive germ cells essential for fertility, and haemopoietic cells, are most vulnerable to radiation, which can depress bone marrow from a dose of about 2 Gy or higher. Haemopoietic cells are the precursor stem cells that later become a wide range of different blood cells in the body.

In previous nuclear disasters and accidents, allogeneic stem-cell transplantation (ie stem cells from a donor) has been used, But this has major limitations, such as time-consuming donor searching, graft failure, graft-versus-host disease (GVHD), or profound immune suppression after transplantation.

Instead of this, the Japanese call for collection of the peripheral blood stem cells (PBSC) of the workers themselves so that they could have future transplants should the need arise. This technique has several advantages over allogeneic transplantation; it does not cause GVHD, and does not require immunosuppressant drugs that make radiation victims even more vulnerable to infection. Further, the technique can more rapidly restore normal haemopoietic functionality in the body, the safety of the collection method is proven, and the cells are easy to freeze and store. Finally, it could be used to treat future leukaemia (a known possibility of radiation exposure) as well as bone marrow defects. But the authors also acknowledge autologous transplant is not perfect since it can rescue injury of bone marrow only and not other tissues, such as gastrointestinal tract, skin, or lung.

The authors say that 107 transplant teams are standing by in Japan to collect and store haemopoietic stem cells from the workers who are striving to restrain the radiation, and more than 50 hospitals in Europe have agreed to help the workers if required. But the Nuclear Safety Commission of Japan is resisting the plan, due to the "physical and psychological burden for nuclear workers", and there being "no consensus among international authoritative bodies, and no sufficient agreement among the Japanese public."

Tanimoto, Taniguchi and colleagues add: "The most important mission is to save the nuclear workers' lives and to protect the local communities. Such an approach would be the industry's best defence: if a fatal accident happened to the nuclear workers, the nuclear power industry of Japan would collapse."

They conclude: "The process to completely shut down the reactors in Fukushima is expected to take years. The risk of accidental radiation exposure will thus accumulate for the nuclear workers and banking of their autologous PBSCs will become increasingly important. A judgment of right or wrong on this scheme must be determined from the standpoint of the nuclear workers and their families, not from a point of view of cost-benefit balance in ordinary times. Toranomon Hospital in Tokyo is ready to harvest and bank autologous PBSCs for the nuclear workers upon request."

Source
The Lancet

Scientists Create Stable, Self-Renewing Neural Stem Cells

In a paper published in the April 25 early online edition of the Proceedings of the National Academy of Sciences, researchers at the University of California, San Diego School of Medicine, the Gladstone Institutes in San Francisco and colleagues report a game-changing advance in stem cell science: the creation of long-term, self-renewing, primitive neural precursor cells from human embryonic stem cells (hESCs) that can be directed to become many types of neuron without increased risk of tumor formation.

"It's a big step forward," said Kang Zhang, MD, PhD, professor of ophthalmology and human genetics at Shiley Eye Center and director of the Institute for Genomic Medicine, both at UC San Diego. "It means we can generate stable, renewable neural stem cells or downstream products quickly, in great quantities and in a clinical grade millions in less than a week that can be used for clinical trials and, eventually, for clinical treatments. Until now, that has not been possible."

Human embryonic stem cells hold great promise in regenerative medicine due to their ability to become any kind of cell needed to repair and restore damaged tissues. But the potential of hESCs has been constrained by a number of practical problems, not least among them the difficulty of growing sufficient quantities of stable, usable cells and the risk that some of these cells might form tumors.

To produce the neural stem cells, Zhang, with co-senior author Sheng Ding, PhD, a former professor of chemistry at The Scripps Research Institute and now at the Gladstone Institutes, and colleagues added small molecules in a chemically defined culture condition that induces hESCs to become primitive neural precursor cells, but then halts the further differentiation process.

"And because it doesn't use any gene transfer technologies or exogenous cell products, there's minimal risk of introducing mutations or outside contamination," Zhang said. Assays of these neural precursor cells found no evidence of tumor formation when introduced into laboratory mice.

By adding other chemicals, the scientists are able to then direct the precursor cells to differentiate into different types of mature neurons, "which means you can explore potential clinical applications for a wide range of neurodegenerative diseases," said Zhang. "You can generate neurons for specific conditions like amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease), Parkinson's disease or, in the case of my particular research area, eye-specific neurons that are lost in macular degeneration, retinitis pigmentosa or glaucoma."

The new process promises to have broad applications in stem cell research. The same method can be used to push induce pluripotent stem cells (stem cells artificially derived from adult, differentiated mature cells) to become neural stem cells, Zhang said. "And in principle, by altering the combination of small molecules, you may be able to create other types of stem cells capable of becoming heart, pancreas, or muscle cells, to name a few."

The next step, according to Zhang, is to use these stem cells to treat different types of neurodegenerative diseases, such as macular degeneration or glaucoma in animal models.

Source: University of California

Autologous Induced Pluripotent Stem Cells And Gene Repair Therapy For Treatment Of Familial Hypercholesterolemia

Study shows, for the first time, the successful reprogramming of diseased human hepatocytes into induced pluripotent stem cells (iPSC).1

Results also found differentiation into mature hepatocytes was more efficient than that with fibroblast-derived iPSCs.

The generation of diseased hepatocyte-derived human iPSC lines provides a good basis for the study of liver disease pathogenesis.

Such technology could give a potentially unlimited reservoir of cells for the treatment of human liver diseases: generating genetically corrected liver cells via auto-transplantation of genetically modified hepatocytes, thus avoiding liver transplant and lifelong immunosuppression.

References:
1 Bosman, A. et al. Progress toward the clinical application of autologus induced pluripotent stem cells and gene repair therapy for treatment of familial hypercholesterolemia. Abstract presented at The International Liver CongressTM 2011.

Source:
Travis Taylor
European Association for the Study of the Liver

Pioneer In Regenerative Medicine For Neurodegenerative Disorders Receives Everfront Award At Stem Cell Conference In Taiwan

Dr. Paul Sanberg, Distinguished University Professor and senior associate vice president for research and innovation at the University of South Florida, received the Everfront Award at the 4th Pan Pacific Symposium on Stem Cell and Cancer Research held earlier this month in Taichung, Taiwan.

The Everfront Award honors outstanding research contributions in stem cell and cancer research, including pre-clinical, clinical and translational work, and is presented to a researcher at the forefront of his or her field. Dr. Sanberg, who also serves as executive director of the USF Center of Excellence for Aging and Brain Repair, has spent decades in stem and cell therapy research.

Dr. Sanberg's stem cell research expertise, his efforts in innovation, technology transfer and translational medicine, and his initiatives in developing academic exchanges between Taiwanese and U.S. researchers were noted by symposium chair Dr. Shinn-Zong Lin, neurosurgeon and superintendant of the China Medical University Hospital. In particular, Dr. Sanberg's pioneering efforts in regenerative medicine for neurodegenerative disorders, capture the award's core criteria, Dr. Lin said.

Dr. Sanberg, a keynote speaker at the symposium, praised Taiwan and the China Medical University Hospital for their globally important research agendas as they work to bring innovative stem cell therapies to the patient's bedside under international standards. Senior officials of both the Taiwanese and South Korean Food and Drug Administrations held open discussions with academic, clinical and industry leaders worldwide at the symposium.

Source:
Randy Fillmore
University of South Florida (USF Health)

Versatility Of Stem Cells Controlled By Alliances, Competitions Of Proteins

to make, stem cells have a process to "decide" whether to transform into a specific cell type or to stay flexible, a state that biologists call "pluripotency." Using a technology he invented, Brown researcher William Fairbrother and colleagues have discovered new molecular interactions in the process that will help regenerative medicine researchers better understand pluripotency.

In a paper published in advance online in the journal Genome Research, Fairbrother's team showed that different proteins called transcription factors compete and cooperate in the cells to produce complex bindings along crucial sequences of DNA. This game of molecular "capture the flag," played in teams and amid shifting alliances, appears to be a necessary part of what determines whether stem cells retain their pluripotency and whether specialized, or differentiated, cells can regain it.

In recent years scientists have reported spectacular successes in turning fully differentiated cells back into pluripotent stem cells, a process called reprogramming. But the animals derived from these cells often suffer higher rates of tumors and other problems, Fairbrother said. The reason may be because the complex details of the reprogramming process haven't been fully understood. He said there are many misconceptions about how reprogramming transcription factors interact with DNA.

"Most people think of a protein binding to DNA as a single, surgical thing where you have this isolated binding event," Fairbrother said. "But in fact we show that sometimes these binding events occur over hundreds of nucleotides so they seem more like great greasy globs of proteins that are forming. In addition, the proteins interact with each other, diversifying their function by appearing in complexes with with different partners at different places."

By employing a high-throughput, high-resolution binding assay that he's dubbed MEGAShift, Fairbrother and his colleagues, who include pathology researchers from the University of Utah School of Medicine, were able to analyze the interactions of several key transcription factors in a region of 316,000 letters of DNA with a resolution as low as 10 base pairs. Through hundreds of thousands of array measurements, lead authors Luciana Ferraris and Allan Stewart, Fairbrother, Alec DeSimone, and the other authors learned previously unspotted patterns of protein interactions.

"How do stem cells stay in the state where they can keep their options open?" Fairbrother said. "A key player is POU5F1. But what are the key players that could interact with it and modulate its function? We've developed technology to look at that question."

One of several findings in the paper concerned POU5F1 and its archrival, POU2F1, which binds to exactly the same eight-letter DNA sequence. Which protein binds to the sequence first influences whether a stem cell specializes or remains pluripotent. Experiments showed that a determining factor was a third protein called SOX2. SOX2 helped both proteins bind, but it helps POU2F1 more than POU5F1. In contrast, the team found that another player, NANOG, exclusively helps POU5F1.

"Who binds next to a protein is a determinant of who ends up binding to a sequence," Fairbrother said.

With support from the National Institutes of Health, Fairbrother's group is also applying MEGAShift to other questions, including how protein-protein interactions affect the formation of RNA-protein complexes, which can be even more complicated than binding DNA.

They will also look at the problem of narrowing the field of hundreds of genomic sequence variations that exist naturally in the population down to the real genetic "causal variants" of disease risk. MEGAShift can sort through which variants associated with disease result in an altered binding event that results in a clinical manifestation, such as diabetes or lupus.

Notes:

In addition to Fairbrother, DeSimone, Ferraris and Stewart, other authors on the paper Matthew Gemberling at Brown, Dean Tantin at the University of Utah, and Jinsuk Kang also at the University of Utah.

The research was funded by the National Human Genome Research Institute.

Source:
David Orenstein
Brown University