Stromal cell-derived factor-1 promotes bone marrow-derived cells differentiation to cardiomyocyte phenotypes in vitro

• Published in: Cell proliferation 2008-04, Vol.41 (2), p.336-347
• Main Authors: Chen, M., Xie, H.-Q., Deng, L., Li, X.-Q., Wang, Y., Zhi, W., Yang, Z.-M.
• Format: Article
• Language: English
• Subjects: Animals; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Cell Differentiation - drug effects; Cells, Cultured; Chemokine CXCL12 - metabolism; Chemokine CXCL12 - pharmacology; Chromones - pharmacology; Heterocyclic Compounds - pharmacology; Humans; Mice; Morpholines - pharmacology; Myocytes, Cardiac - cytology; Myocytes, Cardiac - drug effects; Oncogene Protein v-akt - antagonists & inhibitors; Oncogene Protein v-akt - metabolism; Original; Phenotype; Phosphatidylinositol 3-Kinases - metabolism; Phosphoinositide-3 Kinase Inhibitors; Protein Kinase Inhibitors - pharmacology; Receptors, CXCR4 - antagonists & inhibitors; Receptors, CXCR4 - metabolism; Recombinant Proteins - metabolism; Recombinant Proteins - pharmacology; Structure-Activity Relationship
• ISSN: 0960-7722; 1365-2184
• DOI: 10.1111/j.1365-2184.2008.00519.x

.  Objective: Recent studies have demonstrated the potential of bone marrow‐derived cells (BMDC) to differentiate into cardiomyocytes. Up‐regulation of stromal cell‐derived factor‐1 (SDF‐1), a member of the chemokine CXC subfamily, mediating recruitment of BMDC has been documented in infarcted myocardium; however, it remains unknown whether SDF‐1 plays a role in cardiomyogenesis of BMDC. Materials and methods: Adherent BMDCs were cultured with SDF‐1, or specific inhibitor for PI3K, CXCR4 or Akt with SDF‐1, respectively. After 2 weeks, mRNAs and proteins from BMDCs were examined. Results: Two weeks after supplementation with SDF‐1, either murine or human adherent BMDC cultured in vitro expressed cardiac specific mRNAs (NKX2.5, atrial natriuretic factor and heavy chain β‐myosin) and proteins (troponin I and heavy chain cardiac myosin), and expression levels were partly decreased by combined treatment of CXCR4, PI3K or Akt inhibitor, with SDF‐1. Conclusions: The novel findings suggest that beyond its role in mobilization and homing of BMDC, SDF‐1 can promote BMDC to give rise to cardiomyocyte phenotypes in vitro, and the SDF‐1/CXCR4/PI3K/Akt pathway may be one of the molecular mechanisms regulating cardiomyogenesis.