Abstract 13854: Human Bone Marrow Progenitor Cells Derived From CD271+ Stem Cells Secrete Factors That Improve Cardiac Function After Myocardial Infarction and Activate Adult Resident Cardiac Progenitors
The beneficial effects of administered bone marrow mesenchymal stem cells (BM-MSCs) in cardiac repair after injury are mediated in part by secreted factors from BM-MSCs. In addition to rescuing mature cells from cell death, MSCs may act also by protecting and stimulating resident cardiac progenitor cells (CPs). Recently, we and others demonstrated that a MSC subpopulation can be directly isolated from BM mononuclear cells by CD271. To develop a standardized paracrine-based therapy for acute myocardial infarction (MI), we investigated whether secreted factors from CD271-derived progenitors could preserve cardiac function after MI and protect resident CPs. MSCs were isolated from human BM by magnetic-activated cell sorting against CD271. Serum-free conditioned medium (CdM) was prepared from CD271-sorted MSCs. Mice with MI received intracardiac infusion of CdM or vehicle at 24 hours after coronary artery ligation. TUNEL staining revealed that CdM infusion significantly reduced cell death in the infarcted heart 1 day after the treatment (%TUNEL+ cells, control, 17.2 ± 8.1%; CdM, 3.7 ± 2.2%; p < 0.05). Echocardiographic results demonstrated that CdM infusion ameliorated cardiac dysfunction and remodeling 1 week after MI (%FS, control, 8.9 ± 4.1%; CdM, 20.7 ± 8.1%, p < 0.05; LVEDd, control, 4.5 ± 0.8 mm; CdM, 3.6 ± 0.7 mm; p < 0.05). We cultured adult rat resident CPs in the presence of MSC-secreted factors to determine if they directly protected or activated CPs. CdM from the MSCs significantly improved the survival of CPs exposed to hypoxia compared with CP survival in control medium (p < 0.05), in part through the Jak2/STAT3 pathway. Under normoxic conditions, CPs proliferated in CdM and increased in number (147.5 % of baseline). In contrast, the CPs incubated in serum-free control medium decreased by 45.1%. Notably, the CdM-expanded CPs differentiated into precursors of cardiac myocytes, smooth muscle cells, and endothelial cells. Our results indicate that soluble factors secreted by MSCs isolated from CD271+ BM cells can preserve cardiac function after acute MI by directly reducing the cell death in heart. In addition, factors secreted by MSC may improve cardiac repair after MI by protecting and activating resident cardiac progenitors.
- © 2010 by American Heart Association, Inc.