title: Hypoxic preconditioning improves survival of cardiac progenitor cells: role of stromal cell derived factor-1α-CXCR4 axis.
abstract: BACKGROUND
  Cardiac progenitor cells (CPCs) have been shown to be suitable in stem cell therapy for resurrecting damaged myocardium, but poor retention of transplanted cells in the ischemic myocardium causes ineffective cell therapy. Hypoxic preconditioning of cells can increase the expression of CXCR4 and pro-survival genes to promote better cell survival; however, it is unknown whether hypoxia preconditioning will influence the survival and retention of CPCs via the SDF-1α/CXCR4 axis.
  
  
  RESULTS
  CPCs were isolated from adult mouse hearts and purified by magnetic activated cell sorting using c-kit magnetic beads. These cells were cultured at various times in either normoxic or hypoxic conditions, and cell survival was analyzed using flow cytometry and the expression of hypoxia-inducible factor-1α (HIF-1α), CXCR4, phosphorylated Akt and Bcl-2 were measured by Western blot. Results showed that the expression of pro-survival genes significantly increased after hypoxia treatment, especially in cells cultured in hypoxic conditions for six hours. Upon completion of hypoxia preconditioning from c-kit+ CPCs for six hours, the anti-apoptosis, migration and cardiac repair potential were evaluated. Results showed a significant enhancement in anti-apoptosis and migration in vitro, and better survival and cardiac function after being transplanted into acute myocardial infarction (MI) mice in vivo. The beneficial effects induced by hypoxia preconditioning of c-kit+ CPCs could largely be blocked by the addition of CXCR4 selective antagonist AMD3100.
  
  
  CONCLUSIONS
  Hypoxic preconditioning may improve the survival and retention of c-kit+ CPCs in the ischemic heart tissue through activating the SDF-1α/CXCR4 axis and the downstream anti-apoptosis pathway. Strategies targeting this aspect may enhance the effectiveness of cell-based cardiac regenerative therapy.
authors: Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, China.
authors: Fengdi
authors: F
authors: Yan
authors: Yuyu
authors: Y
authors: Yao
authors: Lijuan
authors: L
authors: Chen
authors: Yefei
authors: Y
authors: Li
authors: Zulong
authors: Z
authors: Sheng
authors: Genshan
authors: G
authors: Ma
mesh_terms: D000818:Animals; D017209:Apoptosis; D015687:Cell Hypoxia; D002465:Cell Movement; D002470:Cell Survival; D064987:Cell- and Tissue-Based Therapy; D054377:Chemokine CXCL12 / Q000378:metabolism*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy; D009206:Myocardium / Q000473:pathology*; D010641:Phenotype; D019718:Receptors, CXCR4 / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology*
chemical_list: D054377:Chemokine CXCL12; D019718:Receptors, CXCR4