Finding Expandable Induced Cardiovascular Progenitor Cells.

Abstract

Expandable Cardiovascular Progenitor Cells Reprogrammed From Fibroblasts Zhang et al Cell Stem Cell . 2016;18:368–381. Lineage Reprogramming of Fibroblasts Into Proliferative Induced Cardiac Progenitor Cells by Defined Factors Lalit et al Cell Stem Cell . 2016;18:354–367. Cardiovascular progenitor cells (CPCs) are a promising cell source for cardiac regenerative therapy because of their ability for self-renewal and differentiation into various cardiovascular cell types beneficial for myocardial repair: cardiomyocytes, smooth muscle cells, and endothelial cells. Previous evaluations of exogenously derived CPCs have focused mainly on their capacity for trilineage differentiation rather than self-renewal because of the lack of an effective protocol to maintain and expand CPCs long-term in culture. In a recent issue of Cell Stem Cell , 2 groups of investigators independently reported their success in isolating, maintaining, and expanding mouse CPCs in culture for >18 to 20 passages (1010- to 1015-fold expansion), with faithful preservation of progenitor phenotype and ability for trilineage-restricted differentiation in both cell culture and mouse models of myocardial infarction (MI). This commentary will discuss the unique findings of these 2 studies, highlight the strengths and weaknesses of each CPC derivation/expansion technique, and propose additional steps necessary to accelerate their clinical translation. The past 2 decades have witnessed some of the most dramatic developments in the field of cardiac regeneration. Central to numerous controversies is the debate on whether certain stem cell types can differentiate into functional cardiomyocytes at a clinically relevant efficiency after implantation for repair of MI. Bone marrow–derived hematopoietic stem cells1,2 and c-kit+ resident cardiac stem cells3 are 2 notable cell types at the center of contention. Although many adult stem cells can still confer modest therapeutic benefits via paracrine effects, the search for a bona fide progenitor cell type that can generate a significant …