Abstract
Rationale: The regenerative potential of the heart is insufficient to fully restore functioning myocardium after injury, motivating the quest for a cell-based replacement strategy. Bone marrow-derived mesenchymal stem cells (MSCs) have the capacity for cardiac repair that appears to exceed their capacity for differentiation into cardiac myocytes. Objective: Here, we test the hypothesis that bone marrow derived MSCs stimulate the proliferation and differentiation of endogenous cardiac stem cells (CSCs) as part of their regenerative repertoire. Methods And Results: Female Yorkshire pigs (n=31) underwent experimental myocardial infarction (MI), and 3 days later, received transendocardial injections of allogeneic male bone marrow-derived MSCs, MSC concentrated conditioned medium (CCM), or placebo (Plasmalyte). A no-injection control group was also studied. MSCs engrafted and differentiated into cardiomyocytes and vascular structures. In addition, endogenous c-kit + CSCs increased 20-fold in MSC-treated animals versus controls (P+ CSCs in MSC versus control (P+ CSCs proliferation into enriched populations of adult cardioblasts that expressed Nkx2-5 and troponin I. Conclusions: MSCs stimulate host CSCs, a new mechanism of action underlying successful cell-based therapeutics.
Original language | English (US) |
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Pages (from-to) | 913-922 |
Number of pages | 10 |
Journal | Circulation Research |
Volume | 107 |
Issue number | 7 |
DOIs | |
State | Published - Oct 1 2010 |
Externally published | Yes |
Keywords
- cardiac stem cells
- mesenchymal stem cells
- myocardial infarction
- myocardial regeneration
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
- Medicine(all)