Protein enables scientists to convert skin to blood vessels

A molecular switch has been identified that converts skin cells into cells found in blood vessels, raising hopes of aiding heart disease sufferers.

This technique boosts levels of an enzyme that keeps cells young and could also potentially help cells avoid ageing as they are grown in the lab. Although this technique has been used before, this is the first time it has been understood by scientists.

Some techniques to convert mature skin cells into pluripotent stem cells use a cocktail of chemicals to ensure they turn into designated cell types. Other methods modify cells, skippingthe stem cell state completely. Recently, researchers have been exploring ‘rewinding’ skin cells so they lose some of their mature cell identity.

Dr Jalees Rehman, who led the study at the University of Illinois at Chicago, said: “They don't revert all the way back to a pluripotent stem cell, but instead turn into intermediate progenitor cells.” Even though they only differentiate into a few different cell types, progenitor cells can be grown in large quantities, making them suitable for regenerative therapies.

Rehman’s research group discovered that progenitor cells could be converted into blood vessel endothelial cells or erythrocytes depending on the level of a gene transcription factor called SOX17. When SOX17 levels were increased, progenitor cells were five times as likely to become endothelial cells. When this process was reversed, fewer endothelial cells but more erythrocytes were produced.

Dr Rehman said: “It makes a lot of sense that SOX17 is involved because it is abundant in developing embryos when blood vessels are forming.” When human progenitor cells were embedded into a gel implanted into mice, the cells formed functional human blood vessels. Mice that were suffering from heart damage formed functional human blood vessels in their hearts – even interlinking with existing murine vessels to improve heart function.

During the course of the research, the scientists observed increased levels of telomerase - the anti-ageing enzyme responsible for telomeres on the ends of chromosome - in progenitor cells. “The increase in telomerase we see in the progenitor cells could be an added benefit of using this partial de-differentiation technique for the production of new blood vessels for patients with cardiac disease, especially for older patients,” said Dr Rehman. “The process of converting and expanding these cells in the lab could make them age even further and impair their long-term function. But if the cells have elevated levels of telomerase, the cells are at lower risk of premature ageing.”

Increased levels of telomerase are also observed in cancer cells, enabling cell division to occur at a very high rate. However, the scientists didn’t observe any tumour formation during their research and their next steps will involve further research over a longer time period in larger animals. The study was published in Circulation.