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Circ Res. 2010 Oct 1;107(7):913-22. doi: 10.1161/CIRCRESAHA.110.222703. Epub 2010 Jul 29.

Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation.

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  • 1University of Miami Miller School of Medicine, Interdisciplinary Stem Cell Institute, Miami, FL 33136, USA.

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<0.001), there was a 6-fold increase in GATA-4(+) CSCs in MSC versus control (P<0.001), and mitotic myocytes increased 4-fold (P=0.005). Porcine endomyocardial biopsies were harvested and plated as organotypic cultures in the presence or absence of MSC feeder layers. In vitro, MSCs stimulated c-kit(+) 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.

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PMID:
20671238
[PubMed - indexed for MEDLINE]
PMCID:
PMC3408082
Free PMC Article

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