Chen M, Xie H-Q, Deng L, Li X-Q, Wang Y, Zhi W, Yang Z-M
Division of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
Cell Prolif. 2008 Apr;41(2):336-47. doi: 10.1111/j.1365-2184.2008.00519.x.
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.
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.
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.
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.
近期研究已证实骨髓来源细胞（BMDC）具有分化为心肌细胞的潜力。趋化因子CXC亚家族成员基质细胞衍生因子-1（SDF-1）的上调介导BMDC的募集，这在梗死心肌中已有记载；然而，SDF-1是否在BMDC的心肌生成中发挥作用仍不清楚。
贴壁的BMDC分别与SDF-1或PI3K、CXCR4或Akt的特异性抑制剂以及SDF-1一起培养。2周后，检测BMDC的mRNA和蛋白质。
补充SDF-1两周后，体外培养的小鼠或人贴壁BMDC表达心脏特异性mRNA（NKX2.5、心钠素和β-肌球蛋白重链）和蛋白质（肌钙蛋白I和心肌肌球蛋白重链），联合使用CXCR4、PI3K或Akt抑制剂与SDF-1处理后，表达水平部分降低。
这些新发现表明，除了在BMDC的动员和归巢中发挥作用外，SDF-1还可在体外促进BMDC产生心肌细胞表型，且SDF-1/CXCR4/PI3K/Akt信号通路可能是调节心肌生成的分子机制之一。
