Human skin tissue, genetically reprogrammed into human-induced pluripotent stem cells (hiPSCs) , was able to inject the cells into rat hearts and get new heart tissue integrated to the rat hearts.
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 today (Wednesday) in the European Heart Journal , opens up the prospect of treating heart failure patients with their own, human-induced pluripotent stem cells (hiPSCs) to repair their damaged hearts. As the reprogrammed cells would be derived 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.
I think we need a legal environment that allows a more aggressive approach to human trials. For someone within 5 years of dying from heart failure the risks (notably cancer) of therapy using hiPSC should be weighed against otherwise inevitable death from heart failure.
The stem cells were derived from older patients with heart disease. This demonstrates a patient's own cells could be reprogrammed to restore damaged tissue.
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 rejection by the immune system. Recent studies have shown that it is possible to derive 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.
The danger is that the reprogrammed cells will become cancerous. But if you otherwise have but a few years left to live you should be allowed to throw the dice and try a stem cell therapy.
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 genes or "transcription factors" (Sox2, Klf4 and Oct4), followed by a small molecule called valproic acid, to the cell nucleus. Crucially, this reprogramming cocktail did not include a transcription factor called c-Myc, which has been used for creating stem cells but which is a known cancer-causing gene.
"One of the obstacles to using hiPSCs clinically in humans is the potential for the cells to develop out of control and become tumours," explained Prof Gepstein. "This potential risk may stem from several reasons, including the oncogenic factor c-Myc, and the random integration into the cell's DNA of the virus that is used to carry the transcription factors – a process known as insertional oncogenesis.
The researchers think we are still 5-10 years away from clinical trials of this approach. I think shows how the regulatory and legal environment causes an excessively conservative and slow approach to development of revolutionary therapies.
|Share |||Randall Parker, 2012 May 24 10:08 PM Biotech Heart Cardiovascular|