Cardiomyocyte proliferation and progenitor cell recruitment underlie therapeutic regeneration after myocardial infarction in the adult mouse heart.
Bottom Line: After MI, new cardiomyocytes arise from both progenitors as well as pre-existing cardiomyocytes.Transplantation of CDCs upregulates host cardiomyocyte cycling and recruitment of endogenous progenitors, while boosting heart function and increasing viable myocardium.The observed phenomena cannot be explained by cardiomyocyte polyploidization, bi/multinucleation, cell fusion or DNA repair.
Affiliation: Cedars-Sinai Heart Institute, Los Angeles, CA, USA.Show MeSH
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Mentions: In order to detect changes in gene expression, we isolated RNA from FACS-sorted GFP+ cardiomyocytes and performed PCR microarray analysis for cell-cycle associated genes. We found that MI upregulated several genes associated with cell-cycle progression in resident cardiomyocytes, the expression of which was further amplified by therapy with CDCs (Fig 6). These genes include ones that orchestrate the G0/G1 transition (Cyclin D1, Cyclin-Dependent Kinase 4), the G1/S transition (Cyclin E, Cyclin-Dependent Kinase 2) and the G2/M transition (Cyclin A1-2, E2F1) (Li & Brooks, 1999; Pasumarthi & Field, 2002). Most of these genes have been shown to be upregulated in the embryonic and neonatal heart (Walsh et al, 2010), which are known to be capable of cardiomyocyte hyperplasia and robust regeneration post-injury (Porrello et al, 2011).
Affiliation: Cedars-Sinai Heart Institute, Los Angeles, CA, USA.