For the first time scientists have succeeded in taking skin cells from heart failure patients and reprogramming them to transform into healthy, new heart muscle cells that are capable of integrating with existing heart tissue. The research, which is published online May 22 in the European Heart Journal, opens up the prospect1 of treating heart failure patients with their own, human-induced pluripotent(多能的) stem cells (hiPSCs) to repair their damaged hearts. As the reprogrammed cells would be derived3 from the patients themselves, this could avoid the problem of the patients' immune systems rejecting the cells as "foreign." However, the researchers warn that there are a number of obstacles to overcome before it would be possible to use hiPSCs in humans in this way, and it could take at least five to ten years before clinical trials could start.
Recent advances in stem cell biology and tissue engineering have enabled researchers to consider ways of restoring and repairing damaged heart muscle with new cells, but a major problem has been the lack of good sources of human heart muscle cells and the problem of rejection4 by the immune system. Recent studies have shown that it is possible to derive2 hiPSCs from young and healthy people and that these are capable of transforming into heart cells. However, it has not been shown that hiPSCs could be obtained from elderly and diseased patients. In addition, until now researchers have not been able to show that heart cells created from hiPSCs could integrate with existing heart tissue.
Professor Lior Gepstein, Professor of Medicine (Cardiology) and Physiology5 at the Sohnis Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine, Technion-Israel Institute of Technology and Rambam Medical Center in Haifa, Israel, who led the research, said: "What is new and exciting about our research is that we have shown that it's possible to take skin cells from an elderly patient with advanced heart failure and end up with his own beating cells in a laboratory dish that are healthy and young -- the equivalent to the stage of his heart cells when he was just born."
Ms Limor Zwi-Dantsis, who is a PhD student in the Sohnis Research Laboratory, Prof Gepstein and their colleagues took skin cells from two male heart failure patients (aged 51 and 61) and reprogrammed them by delivering three genes7 or "transcription factors" (Sox2, Klf4 and Oct4), followed by a small molecule8 called valproic acid, to the cell nucleus9. Crucially, this reprogramming cocktail10 did not include a transcription factor called c-Myc, which has been used for creating stem cells but which is a known cancer-causing gene6.