Progenitor Subpopulations of Valvular Cells Resembling Hematopoietic and Mesenchymal Stem Cells and their Role in Myofibroblastic Activation

Abstract

valvular interstitial cells (qVICs) resembling fibroblasts. In diseased valves, a myofibroblastic phenotype, activated VICs (aVICs), is highly proliferative, synthesize extracellular matrix and repair/remodel the valve. Adult valves also have an understudied small population of progenitor cells (pVIC), which can differentiate into other VIC phenotypes. A better understanding is needed for the role of pVIC in valvular pathophysiology. We hypothesize that pVICs mediate deactivation of VICs, to control or prevent pathological development. Methods: In this study, we isolated two subpopulations of pVICs, Mesenchymal Stem Cells (MSC) and Hematopoietic Stem Cells (HSC), and evaluated their role in myofibroblastic deactivation of VICs. Porcine pVIC subpopulations were magnetically isolated with CD90 and CD34 respectively serving as markers of MSC and HSC. MSC and HSC subpopulations were validated using secondary MSC and HSC markers CD105 and CD117 respectively. Three culture types were designed. Results: A pVIC-supplemented culture was created by increasing pVIC concentration in VIC population by 50% (positive response) Native culture maintained pVIC concentration identical to native valves postharvest (physiologic response). Negative culture had pVICs removed (negative response). Supplemented culture with MSC subpopulation did not have any effect on VIC activation. Supplemented culture with HSC subpopulation induced deactivation in VICs. Conclusion: To our knowledge, this is one of the first observations of pVIC subpopulations mediating myofibroblastic deactivation in VICs and further studies are needed for a more detailed understanding of pVIC function in valvular biology.