“Latest Stem Cells News”

Tweaking the levels of factors used during the reprogramming of adult cells into induced pluriopotent stem (iPS) cells greatly affects the quality of the resulting iPS cells, according to Whitehead Institute researchers.

“This conclusion is something that I think is very surprising or unexpected—that the levels of these reprogramming factors determine the quality of the iPS cells,” says Whitehead Founding Member Rudolf Jaenisch. “We never thought they’d make a difference, but they do.”

An article describing this work is published in the December 2 issue of Cell Stem Cell.

“This conclusion is something that I think is very surprising or unexpected—that the levels of these reprogramming factors determine the quality of the iPS cells,” says Whitehead Founding Member Rudolf Jaenisch. “We never thought they’d make a difference, but they do.”

iPS cells are made by introducing specific reprogramming genes into adult cells. These factors push the cells into a pluripotent state similar to that of embryonic stem (ES) cells. Like ES cells, iPS cells can become any cell type in the body, a characteristic that could make them well-suited for therapeutic cell transplantation or for creating cell lines to study such diseases as Parkinson’s and Alzheimer’s.

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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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Hikers know that moss on a tree trunk always points north. According to new research by Israeli and German scientists, this ancient plant may also provide a new “compass” for stem cell research, telling scientists how better to program stem cells for medical purposes.

Dr. Nir Ohad of Tel Aviv University‘s Department of Plant Sciences and Prof. Ralf Reski of the University of Freiburg have discovered a new use for the Polycomb group proteins (PcG) found in moss. They reported their findings recently in the journal Development. PcG proteins play an important role in telling stem cells how to develop, they believe. The research is being funded by the German-Israeli Foundation.

Moss is a kind of plant that shares basic development processes with those found in humans. “We may not have found the switch that turns stem cells into tissue,” comments Dr. Ohad, “but we have found a key component which makes this switch work.”

In their new paper, the researchers describe an ancient mechanism that alters the way DNA organizes inside the cell nucleus, which in turn, affects gene expression. This finding has important implications in stem cell therapies, which can go awry if implanted stem cells aren’t reprogrammed properly (…)

from http://www.sciencedaily.com/releases/2009/09/090929133242.htm

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Never mind facial masks and exfoliating scrubs, skin takes care of itself. Stem cells located within the skin actively generate differentiating cells that can ultimately form either the body surface or the hairs that emanate from it. In addition, these stem cells are able to replenish themselves, continually rejuvenating skin and hair. Now, researchers at Rockefeller University have identified two proteins that enable these skin stem cells to undertake this continuous process of self-renewal.

The work, published in Nature Genetics, brings new details to the understanding of how stem cells maintain — and lose — their status as stem cells and are able to specialize into various types of cells. It also further dissects a ubiquitous Rube Goldberg-like pathway whose molecular gears and levers play an important role in activating stem cells to divide and transform into tissue-making cells.

Lead researcher Elaine Fuchs, head of the Laboratory of Mammalian Cell Biology and Development, and first author Hoang Nguyen, a former postdoc in the lab, worked with mice engineered to lack the proteins TCF3 and TCF4, which reside in the nucleus of skin stem cells, where they bind to DNA to turn genes off that would otherwise cause the stem cells to differentiate. They found that without TCF3 and TCF4, all of the layers of the mice’s skin still develop properly, but they cannot be maintained.

“The epidermal stem cells — one of the types of stem cells in the skin — lose their capacity to self-renew and replace skin cells that have died,” says Nguyen, who is now an assistant (…)

from http://www.sciencedaily.com/releases/2009/09/090927152828.htm

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Cellular Dynamics International‘s disclosure Wednesday that its researchers have generated stem cells from ordinary human blood samples holds enormous promise in the emerging field of personalized medicine.

The promise in the long term is that, by giving a vial or two of blood, we could all have our own personal stem cells to deploy in the event of a spinal cord injury or the onset of Parkinson’s disease or many other now-incurable diseases.

Cellular Dynamics is the first company to say it can make stem cells from something as readily available, and so representative of human diversity, as blood.

“This stuff sounds like science fiction, but it’s science fact – and we’re doing it in a lab in Madison,” said Bob Palay, the Madison biotech company’s chairman and chief executive.

The discovery will allow the company in the near term to more easily provide a diverse mix of stem cells to researchers to help them understand the basis of disease and how to treat it, he said.

“It opens up all human tissue cells, in all human diversity, to pharmaceutical and academic researchers. It’s so huge, and so few people understand it,” Palay said.

The stem cells, which scientists refer to as induced pluripotent stem cells, or iPS cells, have all the characteristics of embryonic stem cells. They can turn into beating heart cells, liver cells or any other tissue cells in the body.

“From my knowledge of the market, there are companies out there that may be supplying a particular or specific cell type and offering it to industry, but CDI is doing it with a large suite of cells,” said Andy DeTienne, licensing manager for stem cells at the Wisconsin Alumni Research Foundation.

The foundation holds valuable patents on stem cell work done at the University of Wisconsin-Madison and has an ownership stake in Cellular Dynamics.

The company started out selling stem cell-derived heart cells to Roche and other pharmaceutical companies to help them test the toxicity of drugs.

The company has said it hopes to industrialize production of human cell types for research and create a bio-bank in which people could store stem cells engineered from their DNA for use in personalized therapies or in testing reactions to drugs.
Expanded deal with Roche

Cellular Dynamics said this month that it expanded its drug development testing agreement with Roche so that it will be supplying the drug industry giant with more iPS heart cells and other types of cells over the next two years. The companies also will collaborate to perform various tests on the cells.

Cellular Dynamics was formed in 2004 by stem cell pioneer James Thomson and three other UW researchers. The company has 65 employees and finished ramping up its stem cell production facility in June, Palay said. Cellular Dynamics has sales in the “multimillions” of dollars, he said.

Given its early lead in the industry and the additional products Cellular Dynamics is developing, DeTienne said he expects revenue to snowball.
Cellular Dynamics raised $18 million from mostly Wisconsin-based investors late last year.
Palay declined to comment about whether the company is trying to raise more financing.

from JSonline

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Oregon Health & Science University’s unique method of transforming a person’s own skin cells into stem cells has officially been patented. The United States Patent and Trademark Office, an agency within the U.S. Department of Commerce, issued the patent earlier this year. Securing a patent is a key step in commercializing discoveries, an important objective for OHSU. Revenue from commercialized discoveries has the potential to bring financial benefit to the university and the state of Oregon.

The procedure, developed by Shoukhrat Mitalipov, Ph.D. at OHSU’s Oregon National Primate Research Center, accelerated efforts to generate stem cell therapies for humans. The method involves transplanting the nucleus of the cell, which contains an individual’s DNA, to an egg cell that has had its genetic material removed. This cell then develops into stem cells, which are undifferentiated cells that can transform into various other cell types – the building blocks of an organism. For various reasons and despite numerous attempts, previous efforts by others to clone stem cells in primates had failed repeatedly.

When the breakthrough was announced in November 2007, it received worldwide media attention and was named one of TIME Magazine’s top two research achievements of the year. Many also hailed the procedure because it avoided the need for embryonic stem cells. The use of embryonic stem calls has been the subject of debate for many years.

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