Tag Archive for 'Pluripotency'

Induced neural stem cells: Not quite ready for prime time

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

Scientists Reveal How Induced Pluripotent Stem Cells Differ From Embryonic Stem Cells and Tissue of Derivation

The same genes that are chemically altered during normal cell differentiation, as well as when normal cells become cancer cells, are also changed in stem cells that scientists derive from adult cells, according to new research from Johns Hopkins and Harvard.

Although genetically identical to the mature body cells from which they are derived, induced pluripotent stem cells (iPSCs) are notably special in their ability to self-renew and differentiate into all kinds of cells. And now scientists have detected a remarkable if subtle molecular disparity between the two: They have distinct “epigenetic” signatures; that is, they differ in what gets copied when the cell divides, even though these differences aren’t part of the DNA sequence.

“Relatively little study has been done on the epigenetic nature of stem cells,” says Andrew Feinberg, M.D., M.P.H., a professor of medicine at the Johns Hopkins University School of Medicine. “To date, the bulk of what is known about stem cells is focused on how you create them and grow them and so forth, but not on the essence of them, and what is fundamentally different about these cells.”

To compare and contrast mature connective tissue cells called fibroblasts with the pluripotent stem cells into which they were reprogrammed, the investigators focused on a chemical change known as methylation. This chemical change which, associated with silencing genes, is classified as epigenetic because, although not part of the DNA sequence, is copied when a cell divides. They identified and then measured so-called differentially methylated regions (DMRs) of genes whose expression was changed in the process of being reprogrammed from a parent cell to a stem cell.

Building on previous research that looked at where differently methylated sites were located in cancer cells, as well as on research that had shown these same sites matching up with many of the methylated areas that had been implicated in the differentiation of normal brain, liver and spleen tissues, the team discovered that the reprogramming of a cell to become a stem cell apparently involves many of the very same DMRs and genes.

“The surprise,” says Feinberg, “is that there is such a degree of overlap between the differently methylated regions and genes that are involved in turning a fibroblast into a stem cell and turning a normal cell into a cancer cell.”

The study, done jointly with George Q. Daley, M.D., Ph.D., and colleagues from Harvard University, was published Nov. 1 in the advanced online edition of Nature Genetics. The researchers suggest in the study that certain sites throughout the genome appear to be generally involved in distinguishing DNA methylation among different cell types and cancers, and these same sites are involved in reprogramming fibroblasts back into stem cells (…)

from http://newswire.ascribe.org/cgi-bin/behold.pl?ascribeid=20091104.074444&time=09%2059%20PST&year=2009&public=0

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Stem Cells Used to Create New Jaw Bone

Like Samson, researchers in the field of stem cells have used the jawbone to make a point. Dr. Gordana Vunjak-Novakovic and her team at Columbia University have manipulated adult stem cells to grow one of the most difficult sections of bone to replace, the temporomandibular joint. This jawbone was created by allowing pluripotent cells harvested from marrow to grow in a scaffold that was fashioned to mimic the TMJ’s shape.

It is the first accurate and anatomically sized bone created by stem cells in a lab. Dr. Vunjak-Novakovic hopes that this new creation will serve as a proof of concept — if they can make the complex TMJ, they should be able to grow many other bones in your body. While this work is truly amazing, it still has some major hurdles to jump before it could be used to replace damaged or cancerous bones in humans (…)

Growing a fully functional part of the human body depends not only on coaxing adult stem cells to replicate and specialize, it also requires one heck of a nursery. The Columbia team has developed a bioreactor which provides all of the necessary nutrients for stem cells to develop into bone. The shape of the scaffold inside the bioreactor was defined through the use of many digital pictures. Which raises the possibility that eventual bone recipients could have the new body part made to look exactly like the old one. While the bioreactor is top notch, work still has to be done to find a way for the newly created bone to carry its own blood supply that can be easily adapted into the host (…)

from http://singularityhub.com/2009/10/13/stem-cells-used-to-create-new-jaw-bone/

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Veterinarian uses stem cells to heal spinal cord illness

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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STEMCELL Technologies Applauds Feeder-Free Derivation of Human Induced Pluripotent Stem Cells

In a landmark paper, researchers at Stanford University have described a new way to derive human induced pluripotent stem cells (iPSCs) without the use of contaminating mouse feeder cells. Using adipose cells as the starting cell population and mTeSR1, a defined medium that allows the expansion of human embryonic and induced pluripotent stem cells without the use of feeders, the researchers were able to fully reprogram the cells to the pluripotent state.

mTeSR1 is a fully defined medium and is the most widely used feeder-independent method for culturing human pluripotent stem cells, with citations in more than 25 publications.

read more on http://www.reuters.com/article/pressRelease/idUS155006+14-Sep-2009+BW20090914

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