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Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation.
- Source :
-
Circulation research [Circ Res] 2010 Oct 01; Vol. 107 (7), pp. 913-22. Date of Electronic Publication: 2010 Jul 29. - Publication Year :
- 2010
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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.<br />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.<br />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.<br />Conclusions: MSCs stimulate host CSCs, a new mechanism of action underlying successful cell-based therapeutics.
- Subjects :
- Animals
Biopsy
Bone Marrow Cells cytology
Bone Marrow Cells metabolism
Cell Communication physiology
Cell Differentiation physiology
Cell Division physiology
Cells, Cultured
Coculture Techniques
Coronary Vessels cytology
Coronary Vessels physiology
Culture Media, Conditioned pharmacology
Female
Green Fluorescent Proteins genetics
Mesenchymal Stem Cells metabolism
Myocytes, Cardiac metabolism
Proto-Oncogene Proteins c-kit metabolism
Regeneration physiology
Sus scrofa
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells cytology
Myocardial Infarction pathology
Myocardial Infarction therapy
Myocytes, Cardiac cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4571
- Volume :
- 107
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Circulation research
- Publication Type :
- Academic Journal
- Accession number :
- 20671238
- Full Text :
- https://doi.org/10.1161/CIRCRESAHA.110.222703