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Stem cells could drive hepatitis research forward

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Hepatitis C, an infectious disease that can cause inflammation and organ failure, has different effects on different people. But no one is sure why some people are very susceptible to the infection, while others are resistant.

Scientists believe that if they could study liver cells from different people in the lab, they could determine how genetic differences produce these varying responses. However, liver cells are difficult to obtain and notoriously difficult to grow in a lab dish because they tend to lose their normal structure and function when removed from the body.

Now, researchers from MIT, Rockefeller University and the Medical College of Wisconsin have come up with a way to produce liver-like cells from induced pluripotent stem cells, or iPSCs, which are made from body tissues rather than embryos; the liver-like cells can then be infected with hepatitis C. Such cells could enable scientists to study why people respond differently to the infection.

This is the first time that scientists have been able to establish an infection in cells derived from iPSCs — a feat many research teams have been trying to achieve. The new technique, described this week in the Proceedings of the National Academy of Sciences, could also eventually enable “personalized medicine”: Doctors could test the effectiveness of different drugs on tissues derived from the patient being treated, and thereby customize therapy for that patient.

The new study is a collaboration between Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science at MIT; Charles Rice, a professor of virology at Rockefeller; and Stephen Duncan, a professor of human and molecular genetics at the Medical College of Wisconsin.

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Not all cellular reprogramming is created equal

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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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Two Proteins let Skin Cells to return to life

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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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