Abstract 12650: Greater Antiapoptotic, Antiinflammatory, and Proangiogenic Attributes of a Defined Subpopulation of Bone Marrow Mesenchymal Stem Cells May Facilitate Cardiac Repair via Paracrine Effects
Bone marrow mesenchymal stem cells (MSCs) isolated by adherence to plastic are highly heterogeneous. In this study, we tested the hypothesis that an antigenically-defined and homogenous CD45-/c-kit-/Sca-1+/CD90+/CD105- (CD105-) subpopulation of MSCs will exhibit greater angiogenic and antiapoptotic attributes, which may underlie superior cardiac repair by these cells. The CD105- MSCs and their precise antigenic control CD45-/c-kit-/Sca-1+/CD90+/CD105+ (CD105+) MSCs were obtained by two-step FACS isolation and used for comparative analysis of antiapoptotic, inflammatory and angiogenic factor expression. Moreover, the phenotype of sorted MSCs was evaluated by imaging cytometry (ImageStream system). We found that CD105- MSCs expressed higher mRNA levels of VGEF, HGF, and SDF-1, indicating greater ability to induce angiogenesis, when compared with unfractionated MSCs. Consistently, CD105- MSCs formed greater number of endotubules on Matrigel. Importantly, the CD105- MSCs also exhibited reduced expression of proinflammatory agents (TNF-a) and factors involved in adverse cardiac remodeling (MMP-2 and MMP-9) when compared with unfractionated MSCs (Fig.1A). The CD105- MSCs exhibited greater amounts of Bcl-XL, p-Bad, and HO-1, and resisted 2-h hypoxia/2-h reoxygenation-induced apoptosis. The CD105- MSCs also showed greater levels of p-STAT3 and p-ERK1/2, indicating innately higher activation level of cellular antiapoptotic machinery. Along with these functional differences, we also found striking phenotypic differences between CD105- and CD105+ MSCs (Fig.1B), confirming the distinct functional characteristics and a primitive phenotype of CD105- MSCs. We conclude that the CD105- MSCs represent a superior cellular substrate for infarct repair by virtue of their antiapoptotic, antiinflammatory, and angiogenic properties, which collectively contribute to differentiation potential and paracrine activities of these cells.
- © 2012 by American Heart Association, Inc.