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

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


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 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 Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Myocardial Infarction / pathology*
  • Myocardial Infarction / therapy*
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / metabolism
  • Proto-Oncogene Proteins c-kit / metabolism
  • Regeneration / physiology
  • Sus scrofa


  • Culture Media, Conditioned
  • Green Fluorescent Proteins
  • Proto-Oncogene Proteins c-kit