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Induced neural stem cells: Not quite ready for prime time

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University of Wisconsin–Madison
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The great promise of induced pluripotent stem cells is that the all-purpose cells seem capable of performing all the same tricks as embryonic stem cells, but without the controversy.

However, a new study published this week (Feb. 15) in the Proceedings of the National Academy of Sciences comparing the ability of induced cells and embryonic cells to morph into the cells of the brain has found that induced cells — even those free of the genetic factors used to program their all-purpose qualities — differentiate less efficiently and faithfully than their embryonic counterparts.

The finding that induced cells are less predictable means there are more kinks to work out before they can be used reliably in a clinical setting, says Su-Chun Zhang, the senior author of the new study and a professor in the University of Wisconsin-Madison School of Medicine and Public Health.

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Vitamin C Enhances the Generation of Mouse and Human Induced Pluripotent Stem Cells

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Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by defined factors. However, the low efficiency and slow kinetics of the reprogramming process have hampered progress with this technology. Here we report that a natural compound, vitamin C (Vc), enhances iPSC generation from both mouse and human somatic cells. Vc acts at least in part by alleviating cell senescence, a recently identified roadblock for reprogramming.

In addition, Vc accelerates gene expression changes and promotes the transition of pre-iPSC colonies to a fully reprogrammed state. Our results therefore highlight a straightforward method for improving the speed and efficiency of iPSC generation and provide additional insights into the mechanistic basis of the reprogramming process.► Vitamin C improves the speed and efficiency of mouse iPSC generation ► Adding vitamin C converts pre-iPSCs to iPSCs ► Vitamin C alleviates the senescence roadblock to reprogramming ► Human iPSC generation is also improved by vitamin C

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Veterinarian uses stem cells to heal spinal cord illness

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University of California, Davis

With veterinarians across the country training to use stem cells for tendon and ligament repair, a professor at the University of California, Davis (UC Davis) wants to take the technology a step further by applying them to chronic, cell-based diseases.

Richard Vulliet, DVM, is very early into the work. But he is optimistic about the evidence as it exists, of course, and he may have had a success.

Vulliet has treated four dogs with degenerative myelopathy with their own stem cells, which he prefers to call mesenchymal stem cells or pluripotent marrow stromal cells. The terminology has evolved and those names are more descriptive, he says (…)

Vulliet says he got interested in treating these conditions because he was working with mesenchymal stem cells and their interaction with connective tissue, and it was boring. Then he came across two papers.

In one of the papers, Japanese researchers described treating induced cardiomyopathy in experimental rats (Circulation 2005;112:1128-35). They reported that when the cells were injected into the myocardium, function improved, and there was evidence that the cells formed new vascular structures and produced collagen.

In the other paper, researchers at Tulane University in New Orleans induced spine injuries in experimental rats and treated them with mesenchymal stem cells. When they treated the animals immediately after the injury was induced, there was no apparent effect. However, when they waited one week before treating, they found that at five weeks, seven rats out of 12 could lift their trunks with their hind legs. By comparison, none of the 10 rats that were not treated showed similar signs of improvement.

Vulliet says notions of how mesenchymal stem cells might enhance the healing process have expanded beyond the idea that the cells migrate to a site of injury, differentiate into the proper type of cell and incorporate into the tissue. They might modulate immune response as well (…)

Stem cells are an ideal entrée into real-animal research, Vulliet explains. Experiments with human subjects and stem cells are not generally allowed, and federal regulators are unclear about whether they have the authority to regulate such research, since the cells are not drugs and usually are autologous tissue (…)

from http://news.vin.com/VINNews.aspx?articleId=14031

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How To Heal Diabetes Using Stem Cells

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'Diabetes causes amputations', warns poster
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Using skin cells from people with type 1 diabetes, researchers were able to produce cells that made insulin in response to changing blood sugar levels, though not as efficiently as normal insulin-producing cells do. (…) “This is a big deal,” said Susan Solomon, CEO of the New York Stem Cell Foundation, which provided some of the funding for the study. “Tackling the basic biology of type 1 diabetes, which is a very complex disease, is a critical step. With these cells, we can see in a dish what’s happening to the immune system, and if you don’t understand the immune response, you get nowhere with type 1 diabetes.”

“This is very preliminary data, but now we could potentially look at the interaction between immune system cells and insulin-producing cells to find the root cause or trigger, which we think might vary from patient to patient,” explained Meri Firpo, an assistant professor at the Stem Cell Institute at the University of Minnesota (…)

In the current study, researchers from the Howard Hughes Medical Institute at the Harvard Stem Cell Institute and the Naomi Berrie Diabetes Center at Columbia University, obtained skin samples from two white males who had type 1 diabetes. One was diagnosed at 3 years of age, while the other was first diagnosed when he was 21.

Normal skin cells are already specialized cells. Their job is to protect the body with a covering of skin, explained Firpo. To transform these cells into embryonic-like stem cells, essentially getting them back to the beginning when they weren’t already specialized, researcher Doug Melton and his colleagues used three inserted genes to reprogram the cells, creating what’s known as an induced pluripotent stem cell (iPS). In this case, the cells were then turned into insulin-producing cells (…)

She said that this study helps further at least two areas of research that JDRF is focusing on: developing a self-source for islet-cell transplants and blocking the immune response. Another area of research that JDRF is actively pursuing is the possible encapsulation of islet cells before transplantation so that they could hide from the immune system (…)

from http://www.ajc.com/health/content/shared-auto/healthnews/diab/630511.html

A study published today in the Proceedings of the National Academy of Sciences describes a way to create induced pluripotent stem (iPS) cells from ordinary adult cells taken from patients with type 1 diabetes. These stem cells then can be reprogrammed to produce all of the cell types relevant to the disease.

“What you get is the ability to watch, for the first time, type 1 diabetes develop,” says senior author Douglas Melton, a professor of natural sciences at Harvard University and co-director of the Harvard Stem Cell Institute. “Until you watch a disease develop, you will not understand the mechanism, and you therefore cannot devise any kind of sensible treatment or cure.”

Melton and his colleagues show that the reprogrammed iPS cells–so called for their ability to give rise to many cell types–can be spurred to differentiate into tissue resembling the insulin-producing pancreatic beta cells that are destroyed by the immune system in type 1 diabetes.

Embryonic stem (ES) cells have long been the gold standard for deriving pluripotent cell lines. But ES cells can only be used to create disease models for disorders such as cystic fibrosis, where the genetic underpinnings are straightforward. Because the genetics underlying type 1diabetes are complex and poorly understood, researchers have no way to identify diabetes-specific ES cells (…)

Ultimately, Melton plans to construct a “living test tube” for probing the interplay between the beta cells and the immune system in diabetes. He hopes to use the diabetic iPS cells to generate all three relevant cell types and then to put those cells into a so-called humanized mouse that can accept human cells to see how they interact.

from http://www.technologyreview.com/biomedicine/23335/

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