Researchers Mark Progress in Reprogramming
Skin Cells Into Heart Muscle
Reporting on collaborative effort from labs including
THI Stem Cell Engineering
Houston, Texas (July 24, 2012) – Physicians and scientists at the Texas Heart Institute (THI) at St. Luke's Episcopal Hospital (SLEH), working collaboratively with the University of Houston (UH), the Texas A&M Health Science Center in Houston and the Baylor College of Medicine, have shown a new way to convert human skin cells into beating heart cells, according to an article being published in the prestigious Proceedings of the National Academy of Sciences.*
Researchers believe this is an important new and unique step toward being able to repair damage from heart attacks in human hearts, which have very little regenerative capability on their own.
The team, led by Robert J. Schwartz, PhD, director of Stem Cell Engineering at THI and director of UH's Center for Molecular Medicine and Experimental Therapeutics, used human skin cells called fibroblasts, and treated them with ETS2 and MESP1, two human genetic transcription factors that play important roles in the genetic network that produces cardiovascular tissues.
The skin cells were converted into progenitors of "cardiomyocytes"—beating heart muscle cells—within a period of weeks. (Progenitors can differentiate to form one or more kinds of cells.)
"Our study showed that only two factors, ETS2 and MESP1, were needed to reprogram human foreskin dermal fibroblasts into cardiac progenitors within a few days in tissue culture. Neither factor by itself was capable of converting fibroblasts into cardiac cells. These progenitors go on to express the 4 to 5 genes that Olson's and Srivastava's labs showed were critical for repairing damaged mouse hearts. Besides being on top of the regulatory hierarchy, ETS2 and MESP1 converted human skin cells into intermediate staged myocytes, as you would find in early staged embryonic hearts. Our study also used ETS2 and MESP1 proteins that can enter fibroblasts to convert non-cardiogenic cells into myocytes, thus avoiding viral infections. We are moving quickly to determine whether ETS2 and MESP1 proteins can convert cardiac fibroblasts and mesenchymal stem cells that are resident in damaged hearts into cardiac progenitors for long-term repair," Dr. Schwartz explained.
It is expected that the research will provide future opportunities for cell therapies and heart regeneration. The hope is that physicians will be able to convert a patient's own skin cells into new heart muscle tissue to replace heart muscle damaged by a heart attack.
Others, including a team led by Dr. Eric Olson of the University of Texas Southwestern Medical Center in Dallas, have recently reported the ability to use four other transcription factors in combination to convert cardiac fibroblasts in vivo into "functioning cardiac-like myocytes" in laboratory mice with experimentally created heart attacks. Another team affiliated with the University of California San Francisco also published a similar study earlier this year.
"One of the great needs in repairing the human heart is to find a practical and safe means of generating new heart muscle cells," said Dr. James T. Willerson, THI's president and medical director and one of the lead investigators on the research team. "We will now have to see how stable and safe these cells are over time in animal models, but it is significant that we have these new paths to follow along the road to potential new therapy where there have been none before. Whether these strategies are ultimately safe in the human heart is now the question, but these are potentially very major steps forward."
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* PNAS Early Edition: Transcription factors ETS2 and MESP1 transdifferentiate human dermal fibroblasts into cardiac progenitors http://www.pnas.org/content/early/2012/07/18/1120299109.abstract
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Texas Heart Institute at St. Luke's Episcopal Hospital
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Texas Heart Institute at St. Luke's Episcopal Hospital
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