Two Genes Reprogram Skin Cells into Heart Muscle Cells


Researchers at the Texas Heart Institute at St. Luke’s Episcopal Hospital, in collaboration with the University of Houston, Texas A&M Health Science Center in Houston and Baylor College of Medicine have discovered a remarkably simple way to repair damage from heart attacks in human hearts.

The research team was led by Robert Schwartz, who is the director of stem cell engineering at the Texas Heart Institute a the director of the University of Houston’s Center for Molecular Medicine and Experimental Therapeutics. The main finding of this research showed that particular human skin cells called fibroblasts can be treated with two genes called ETS2 and MESP1 that encode transcription factors known to play important roles in the developmental pathway that leads to cardiovascular tissues. This technique turned skin cells into beat heart muscle cells within two weeks.

Skin fibroblasts were used in this study, but another cell line was also used and that was human foreskin fibroblasts and these two genes (ETS2 and MESP1) could convert these cells into cardiac progenitor cells in only a few days.

Neither gene could convert fibroblasts by themselves into heart cells, but together, ETS2 and MESP1 induced the expression of four-five genes known to be critical for repairing damaged mouse hearts. The reprogramming of fibroblasts with ETS2 and MESP1 converted human skin cells into the kind of intermediate staged muscle cells that you would normally observe in an early staged embryonic heart.

Because introducing genes into cells requires the use of viruses that can sometimes cause mutations in cells, Schwartz and his collaborators and colleagues used specially modified ETS2 and MESP1 proteins that could penetrate the cell membrane of fibroblasts. In culture, the these proteins also converted fibroblasts into heart muscle cell progenitors.

According the Schwartz, “We are moving quickly to determine whether ETS2 and MESP1 proteins can convert cardiac fibroblasts and mesenchymal stem cell [sic] that are resident in damaged hearts into cardiac progenitors for long-term repair.” The hope is to eventually convert a patient’s own skin cells into heart muscle cells that will be used to heal their damaged heart.

James T. Willerson, the president and medical director of the Texas Heart Institute, said: “One of the great needs in repairing the human heart is to find a practical and safe means of generating new heart muscle cells. 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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mburatov

Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).