Bone marrow-derived stem cell interactions with adult cardiomyocytes and skeletal myoblasts in vitro

Richard Baffour, Rajbabu Pakala, David Hellinga, Michael Joner, Petros Okubagzi, Stephen E. Epstein, Ron Waksman

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Background and Objectives: Secreted growth factors and cell-to-cell contact are both required to elicit cellular functions. We tested the hypothesis that bone-marrow-derived growth factors, together with cell-to-cell contact between bone-marrow-derived stem cells and cardiomyocytes or myoblasts, promote the proliferation of cardiomyocytes and myoblasts. Methods: Human cardiomyocytes or skeletal myoblasts were cultured for 4 days in the presence of low and high concentrations of bone-marrow-derived mononuclear cell conditioned medium (MNC-CM) or marrow stromal cell conditioned medium (MSC-CM). The concentrations of vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), hepatocyte growth factor (HGF), and insulin-like growth factor-1 in their respective conditioned media were assayed by enzyme-linked immunosorbent assay. Stem cells were mixed with cardiomyocytes or skeletal myoblasts at a 1:1 ratio and cultured for 7 days to assess the proliferation of these cells. In parallel experiments, equal numbers of various cell types were cultured alone. Results: The concentrations of VEGF, MCP-1, and HGF increased in MNC-CM and MSC-CM. MNC-CM showed no effect on cardiomyocyte proliferation. A low concentration of MSC-CM increased cardiomyocyte proliferation by 60% (P<.05). Low concentrations of MNC-CM or MSC-CM showed a trend toward an increased proliferation of myoblasts. A high concentration of either conditioned medium showed a toxic effect. In contact coculture, the proliferation of cardiomyocytes and MNC showed no synergistic effect; instead, there was some evidence of inhibition. The proliferation of cardiomyocytes and stromal cells showed an additive effect. Myoblasts in contact coculture with MNC or MSC showed no synergistic effect. Conclusion: These in vitro results suggest that paracrine effects may be the mechanism by which stromal cells become beneficial in cardiac therapy. MNC do not induce the proliferation of cardiomyocytes. Stem-cell-secreted growth factors induce the proliferation of myoblasts, which is not influenced by cell-to-cell contact.

Original languageEnglish
Pages (from-to)222-230
Number of pages9
JournalCardiovascular Revascularization Medicine
Volume7
Issue number4
DOIs
StatePublished - Oct 2006
Externally publishedYes

Keywords

  • Cardiomyocytes
  • Myoblasts
  • Stem cells

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