“Latest Stem Cells News”

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

Whitehead Institute researchers have developed a novel method of removing potential cancer-causing genes during the reprogramming of skin cells from Parkinson’s disease patients into an embryonic-stem-cell-like state. Scientists were then able to use the resulting induced pluripotent stem (iPS) cells to derive dopamine-producing neurons, the cell type that degenerates in Parkinson’s disease patients.

The work marks the first time researchers have generated human iPS cells that have maintained their embryonic stem-cell-like properties after the removal of reprogramming genes. The findings are published in the March 6 edition of the journal Cell.

Removing the reprogramming genes is also important because of those genes’ effect on an iPS cell’s gene expression (a measure of which genes the cell is using and how much it’s using those genes). When the researchers compared the gene expressions of human embryonic stem cells to iPS cells with and without the reprogramming factors, iPS cells without the reprogramming genes had a gene expression closer to human embryonic stem cells than to the same iPS cells that still contained the reprogramming genes.

“The reprogramming factors are known to bind to and affect the expression of 3,000 genes in the entire genome, so having artificial expression of those genes will change the cell’s overall gene expression,” Dirk Hockemeyer, who is also a co-author of the Cell article. “That’s why the four reprogramming genes can mess up the system so much. From now on, it will be tough for researchers to leave the reprogramming genes in iPS cells.”

from http://web.mit.edu/newsoffice/2009/parkinsons-stem-0305.html

The prospect of treating genetic diseases with corrected stem cells grown from patients’ own bodies has moved closer, after the results of a remarkable experiment.

Scientists have successfully reprogrammed skin tissue from people with a rare form of anaemia to create powerful stem cells, while at the same time rectifying the genetic defect that causes the condition.

The corrected stem cells could be grown into blood precursor cells for therapy. As these would carry a patient’s own DNA, except for the mutation responsible for the illness, they could be transplanted without risk of rejection by the body’s immune system.

Though the research team, from Spain and the United States, has yet to use the cells to treat patients, and several important hurdles still remain, the achievement has been hailed as a significant advance for stem cell research.

It suggests that it should eventually be possible to treat many inherited conditions by making disease-free stem cells from their own bodies. (…)

The cells were infected with a genetically modified virus to correct the gene that causes Fanconi anaemia. These were then reprogrammed into an embryo-like state by modifying further genes, to create versatile master cells known as induced pluripotent stem cells (IPS cells). (…)

Chris Mathew, Professor of Molecular Genetics at King’s College London, said: “This is an important development for families with this rare, inherited blood disorder. The patients have low numbers of blood stem cells in their bone marrow, so there are very few target cells to correct by gene therapy.

“The new research shows that it is possible to reprogramme skin cells from these patients into stem cells in which the genetic defect has been corrected. In future it may become possible to transfer the corrected stem cells back into the patient, but much work remains to be done.”

Read full article on Times Online

Helen Blau

Scientists have now shown that skin cells can be coaxed to behave like muscle cells and muscle cells like skin cells.
The fickleness of the cells, and the relative ease with which they make the switch, provide a glimpse into the genetic reprogramming that must occur for a cell to become something it’s not.

“We’d all like to understand what happens inside the black box (cell),” said Helen Blau, professor and member of Stanford University’s Stem Cell Biology and Regenerative Medicine Institute and co-author of a new study on the subject.
Harnessing these genetic makeovers will allow scientists to better understand how to induce specialised adult cells to revert to a stem-cell-like state in a process called induced pluripotency (iPS).

But Blau’s experiments suggest an intriguing alternative to iPS: that of enticing specialised adult cells to switch identities without requiring a dip into the stem cell pool.
Blau, who heads the Baxter Lab at Stanford University and her lab members fused mouse muscle cells with human skin cells, to create hybrids called heterokaryons.

Hebrew University of Jerusalem

Researchers at the Hebrew University of Jerusalem discovered a method to potentially eliminate the tumor-risk factor in utilizing human embryonic stem cells, said the university on Wednesday.
The researchers’ work paves the way for further progress in the promising field of stem cell therapy, said the press release of the university sent to Xinhua.

According to the release, human embryonic stem cells are theoretically capable of differentiation to all cells of the mature human body (and are hence defined as “pluripotent“).
This ability, along with the ability to remain undifferentiated indefinitely in culture, make regenerative medicine using human embryonic stem cells a potentially unprecedented tool for the treatment of various diseases, including diabetes, Parkinson’s disease and heart failure.

Mental retardation, altered facial characteristics, and heart problems are all problems suffered by children affected by Costello syndrome, a genetic disease that is being studied by researchers in Milan at the Italian Foundation for Cancer Research (FIRC) Institute of molecular oncology (IFOM) using the zebrafish as a model.

The cause of the disease – explained the scientists in the January issue of ‘Disease Models & Mechanisms’ monthly magazine – is a mutation of the Ras gene, the same alteration observed in 20pct of tumors. One out of every five cases of cancer and the rare genetic disease have a common thread.

The credit for the discovery also goes to the zebrafish, an important animal among the most popular in laboratories worldwide, since it is versatile, transparent, and mainly, genetically similar to humans. The mutation of the Ras gene responsible for the Costello syndrome – according to a study supported by the Italian Association for Cancer Research (AIRC) – is manifested in the patient’s germ cells.