November 25, 2009, Updated September 13, 2012

Israeli scientists have developed a way to create beating heart cells with skin cells reprogrammed to become stem cells, making it possible to one day clinically repair a damaged heart.

 

Israeli scientists have discovered a way to create beating heart cells using human skin cells reprogrammed to become stem cells. The findings could lead to advances in disease research, and could in theory be used to repair damaged or diseased tissues.

Published in the latest issue of Circulation, the findings by Professor Lior Gepstein of the Technion-Israel Institute of Technology could make it possible to clinically repair damaged human hearts.

Such an application is at least 10 to 20 years away, says Gepstein, but the process can already be utilized for in-depth study of genetic diseases and the development of personalized drugs for irregular heartbeats and other inherited disorders.

Transforming our cells through reprogramming

The team’s work is based on the research of Japanese scientists followed by other groups, who generated “induced pluripotent stem cells” (iPSCs) from adult mouse and human skin cells. The iPSCs can be turned into almost any type of body cell – something that experts previously thought possible only with embryonic stem cells – and could, in theory, be used to repair damaged or diseased tissues.

Taking a patient’s own cells and turning them into iPSCs for use in tissue repair and regeneration would also eliminate the risk of rejection by the body.

Gepstein and his team from Technion’s Rappaport Faculty of Medicine and Rambam Medical Center used reprogrammed iPSCs derived from healthy human subjects’ skin cells with the characteristics of pluripotent embryonic stem cells. They were then able to convert them into heart cells with all the necessary properties such as expression of heart-related genes, spontaneous electrical activity, mechanical contraction, and response to various hormones such as adrenaline.

According to Gepstein, the rejuvenation of human cells and their transformation into iPSCs can be accomplished with almost any human cell.

Making heart headlines

Nearly eight years ago, Gepstein and colleagues made headlines by creating beating cardiac tissue in the lab from human embryonic stem cells. In 2007, he teamed with the Technion’s Dr. Shulamit Levenberg to create tiny blood vessels within the tissue. This breakthrough could eventually make it possible to implant the tissue in a diseased human heart.

The findings could also someday lead to advances in research on diseases caused by single-gene mutations. The list of these diseases includes familial arrhythmogenic syndromes leading to irregular heartbeat and sudden cardiac death, cardiomyopathies that weaken the heart muscle, and several neurodegenerative disorders.

Certain challenges exist, however. One hazard of using iPSCs as well as ordinary embryonic stem cells is the possibility that the cells will begin to divide wildly and turn cancerous. As a result, “it will be years before they are used clinically,” says Gepstein. While animal studies could eventually lead to clinical work, scientists would first have to learn how to make large amounts of the iPSC-derived heart cells, he concludes.

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