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Stem Cells Could Offer New Source for Skin Grafts

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Researchers are now one step closer to being able to use skin tissue derived from stem cells for the treatment of burn victims, according to a study published November 21 in The Lancet.

By tweaking the way the cells are grown in a Petri dish, a team of scientists at the Institute for Stem Cell Therapy and Exploration of Monogenic Diseases near Paris, France, was able to coax human embryonic stem cells into becoming multilayered skin tissue. The group also grafted the human stem cell-derived skin onto the backs of five mice. The foreign tissue grew well for at least 12 weeks, suggesting that it could at least be a safe temporary solution until skin tissue from a patient’s body, aka autologous graft tissue, is ready.       

The typical treatment for burns involves collecting skin stem cells present in the lower, or basal, layer of skin, and growing enough of them in the lab to cover the area damaged by a burn. The process takes at least three weeks. In the meantime, patients usually receive either cadaver skin or a semi-synthetic cocktail of cells and collagen, both of which, the authors wrote, can trigger rapid rejection by the recipient’s immune system. The drawbacks to the current system—the wait time for permanent skin and the risk of rejection associated with the temporary fixes—could be overcome using human embryonic stem cell-derived skin cells.

To develop a system to create skin cells from human embryonic stem cells, the researchers started with a line from the National Stem Cell Bank in Madison, Wisc. These stem cell lines grow for long periods of time in a Petri dish without losing their pluripotency, or ability to become any type of cell in the body. The team placed the cells on a scaffold so that, as they started to grow layers, only the bottom layer would be in contact with liquid growth medium. This environment simulates the skin, where the bottom layers are exposed to tissue and the top to air.

The trick to making skin cells was to find, what the authors called, the "pharmacological treatment," consisting of the right combination of chemicals and proteins, and to leave cells in this concoction for 40 days. At the end of the treatment period, the group obtained an epithelium consisting of multiple layers that resembled human skin and had the same biological properties.

Although the 40-day treatment is lengthier than the process to make autologous graft tissue, skin cells made from stem cell lines could presumably be made ahead of time in batch and stored for different patients. The authors were able to freeze the skin cells and then re-grow them after thawing.

In order for a stock of stem cell-derived skin to be a viable option for treating burn victims, the immune systems of these patients must not recognize the tissue as foreign and, thus, try to reject it. When the authors examined the different proteins present in their artificial skin, they found only very low amounts of the proteins that are responsible for tissue rejection. Normally, if these proteins, which sit on the surface of cells, are not identical between the donor and recipient, the tissue will be rejected. The absence of this protein is specific to stem cells from embryos. The authors note that skin cells from aborted fetuses also possess low levels of this surface protein.

In addition to tissue rejection, a major concern with human embryonic stem cells for cell replacement therapy has been the potential of the stem cell-derived tissue to be cancerous. The authors did not observe formation of tumors in the grafted mice. In a commentary on the article in the same issue of The Lancet, Holger Schlüter and Pritinder Kaur, at the Epithelial Stem Cell Biology Laboratory at the Peter MacCallum Cancer Centre in Melbourne, Australia, wrote that the long culture time of the cells could have helped reduce the potential for forming tumors in mice.

While the use of human embryonic stem cell-derived skin cells for burn victims awaits clinical studies in humans, Schlüter and Kaur wrote that the study is "is an important advance in the development of therapies for patients with large skin deficits." The researchers add that these skin cells could eventually also help people with epidermolysis bullosa, an inherited condition that causes the skin to blister after minor injuries.

Image courtesy of iStockphoto/dra_schwartz





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