miRNAs Induce Fibroblasts to Reprogram to Cardiomyocytes
Administration of microRNAs into ischemic mice results in conversion of fibroblasts to myocytes
FRIDAY, April 27 (HealthDay News) -- Micro (mi)RNAs can induce cardiac fibroblasts to reprogram to cardiomyocyte-like cells, according to an experimental study published online April 26 in Circulation Research.
Noting that an effective method for repopulation of an injured heart with functional cardiomyocytes would be direct conversion of injured areas, Tilanthi M. Jayawardena, Ph.D., from the Duke University Medical Center in Durham, N.C., and colleagues investigated whether specific miRNAs could induce cardiac fibroblasts to cardiomyocytes in vitro and in vivo.
The researchers identified a combination of miRNAs that were capable of triggering direct cellular reprogramming of fibroblasts to cardiomyocyte-like cells in vitro. Transient transfection of the miRNAs reprogrammed the cells, as noted by expression of mature cardiomyocyte markers, sarcomeric organization, and exhibition of the cardiomyocyte-like phenotypic spontaneous calcium flux. JAK inhibitor 1 treatment enhanced miRNA-mediated reprogramming 10-fold. Administration of miRNA into ischemic mouse myocardium led to evidence of a direct switch of fibroblasts to cardiomyocytes in situ. Genetic tracing analysis suggested that the induced cells were most likely of fibroblastic origin.
"The findings from this study provide proof-of-concept that miRNAs have the capability of directly converting fibroblasts to a cardiomyocyte-like phenotype in vitro," the authors write. "Also of significance is that this is the first report of direct cardiac reprogramming in vivo. Our approach may have broad and important implications for therapeutic tissue regeneration in general."