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


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 beta-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.
Chen
M
M
Division of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
Xie
H-Q
HQ
Deng
L
L
Li
X-Q
XQ
Wang
Y
Y
Zhi
W
W
Yang
Z-M
ZM
D000818:Animals; D001596:Benzylamines; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism / Q000494:pharmacology*; D002867:Chromones / Q000494:pharmacology; D000080027:Cyclams; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects*; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship
D001596:Benzylamines; D054377:Chemokine CXCL12; D002867:Chromones; D000080027:Cyclams; D006571:Heterocyclic Compounds; D009025:Morpholines; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D019718:Receptors, CXCR4; D011994:Recombinant Proteins; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C088327:plerixafor