May 23, 2012
Human Skin Cells Turned Into Healthy Heart Muscle
Scientists on Wednesday reported that they have for the first time taken skin cells from heart attacks patients and turned them into healthy heart tissue that could hopefully be used to one day repair damaged heart muscle.
The healthy, beating heart tissue was grown successfully in the lab from human-induced pluripotent stem cells (hiPSCs), and while scientists said they were not safe enough to put back into human patients, they appeared to work well with other cells when implanted into rats. HiPSCs are a recently discovered source far less controversial than use of embryonic stem cells. And, because the transplanted hiPSCs come from the individual, it could resolve the problems seen with tissue and organ rejection.
While the technique has shown promise in rats, the scientists say there are numerous obstacles to overcome and it could take up to ten years or longer before clinical trials could be available for humans. Even so, it is a significant advance in the quest for replacement cell therapy for heart failure patients.
“More people are surviving following a heart attack than ever before and therefore the number of people living with a damaged heart and heart failure is increasing,” Nicholas Mills, a consultant cardiologist at Edinburgh University, told The Guardian. “Unfortunately, the body has only very limited capacity to repair the heart following a heart attack. There is therefore an urgent need to develop effective and safe treatments to regenerate the heart.”
Recent research has shown that hiPSCs could be derived from young and healthy people and are capable of transforming into heart cells. However, researchers have not been able to obtain those cells from elderly and diseased patients. And until now, researchers have not been able to show that heart cells created from hiPSCs could integrate with existing heart tissue.
“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,” said lead researcher Professor Lior Gepstein, of Sohnis Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine, Technion-Israel Institute of Technology and Rambam Medical Center in Haifa, Israel.
For their study, published in the European Heart Journal, Limor Zwi-Dantsis, a PhD student in the Sohnis Research Laboratory, Gepstein and colleagues took skin cells from two male heart failure patients (ages 51 and 61) and reprogrammed them with three genes (Sox2, Klf4 and Oct4), followed by a small molecule (valproic acid) to the cell nucleus.
The team also used an alternative strategy that involved a virus that delivered reprogramming information to the cell nucleus but which was capable of being removed afterward to avoid insertional oncogenesis.
Using these methods, the hiPSCs were able to differentiate to become cardiomyocytes (heart muscle cells) just as effectively as hiPSCs that had been developed from healthy, young volunteers. The researchers were then able to make cardiomyocytes develop into heart muscle tissue, which they cultured together with pre-existing cardiac tissue. The tissues were beating together within 48 hours, said the researchers.
The researchers transplanted the new tissue into the hearts of healthy rats and found that the grafted tissue started to establish connections with the cells in the host tissue.
“In this study we have shown for the first time that it´s possible to establish hiPSCs from heart failure patients -- who represent the target patient population for future cell therapy strategies using these cells -- and coax them to differentiate into heart muscle cells that can integrate with host cardiac tissue,” said Gepstein.
“We hope that hiPSCs derived cardiomyocytes will not be rejected following transplantation into the same patients from which they were derived. Whether this will be the case or not is the focus of active investigation,” he added. “One of the obstacles in dealing with this issue is that, at this stage, we can only transplant human cells into animal models and so we have to treat the animals with immunosuppressive drugs so the cells won't be rejected.”
“This technology needs to be refined before it can be used for the treatment of patients with heart failure, but these findings are encouraging and take us a step closer to our goal of identifying an effective means of repairing the heart and limiting the consequences of heart failure,” Mills, who was not involved in the study, added.
Gepstein and colleagues plan to continue their research, which includes evaluating the use of hiPSCs in cell therapy and tissue engineering strategies for repairing hearts in various animal models, investigating inherited cardiac disorders, and drug development and testing.
“The European Heart journal is proud to publish this exciting study which opens the door for a novel approach in regenerative medicine,” said the journal´s Editor-in-Chief Thomas LÃ¼scher, Professor and Chairman of Cardiology at the University Hospital Zurich and Director of Cardiovascular Research at the Institute of Physiology of the University Zurich, Switzerland.