The adult human heart has almost no regenerative capacity and forms fibrous, non-contractile scar tissue lacking muscle or blood vessels following a myocardial infarction. Fibroblasts account for a majority of cells in the heart and are activated following injury to form this fibrotic scar tissue. Fibrosis impedes regeneration of cardiac muscle cells, and contributes to loss of contractile function, ultimately leading to heart failure and death. Therapeutic strategies to promote new muscle formation, while limiting fibrosis, represent an attractive approach for heart repair.
Eric N. Olson, Ph.D., and colleagues from UTSW have shown that four gene-regulatory proteins — GATA4, HAND2, MEF2C, and TBX5 (GHMT) — can convert cardiac fibroblasts into beating cardiac-like muscle cells. Introduction of these proteins into proliferating fibroblasts in mice reprograms them into functional cardiac-like myocytes, improving cardiac function and reducing fibrosis and adverse remodeling of the heart following myocardial infarction. The new reprogramming strategy may provide a novel means of improving cardiac function following injury, bypassing many of the obstacles associated with cellular transplantation.
LoneStar Heart Inc. has acquired exclusive worldwide rights from UTSW to this new technology aimed at reprogramming cardiac fibroblasts.
Song, K., Nam, Y.-J., Luo, X., Qi, X., Tan, W., Huang, G. N., Acharya, A., et al. 2012;469:599-604. Heart repair by reprogramming non-myocytes with cardiac transcription factors. Nature. doi:10.1038/nature11139.