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骨髓基质干细胞(bone marrow stromal cells,BMSCs)被认为是能够使梗死心肌再生并恢复受损心功能的有前途的细胞源之一。但是其在梗死部位的低存活率极大地限制了它的临床应用前景。有报道显示基质细胞源性因子-1α(stromal cell derived factor-1α,SDF-1α)能够抑制如内皮前体细胞、胚胎干细胞等的凋亡。但是目前对于SDF-1α能否抑制缺氧和无血清诱导的骨髓基质干细胞的凋亡及其具体机制尚不清楚。本研究中,我们证实,SDF-1α在0.5～2.0μg/m1的浓度时能够通过线粒体通路有效地抑制缺氧和无血清诱导的干细胞的凋亡。SDF-1α抑制线粒体膜电位的升高、抑制细胞色素c从线粒体释放到胞浆,以及降低caspase 3的活性。我们进一步的研究发现PI3K抑制剂Wortmannin和ERK1/2抑制剂U0126能抵消SDF-1α对于线粒体通路的作用。结果显示SDF-1α抑制缺氧和无血清诱导的干细胞凋亡是通过PI3K/Akt和ERK1/2信号通路实现的。同时也提示SDF-1α所介导的这种抗凋亡作用对于细胞移植也将是有益的。
Bone marrow stromal cells (BMSCs) are considered as one of the promising sources of cells that can regenerate infarcted myocardium and restore damaged cardiac function. However, its low survival rate in the infarct greatly limits its clinical application prospects. It has been reported that stromal cell derived factor-1α (SDF-1α) can inhibit the apoptosis of endothelial progenitor cells, embryonic stem cells and the like. However, whether SDF-1α can inhibit apoptosis of bone marrow stromal cells induced by hypoxia and serum-free and its specific mechanism is still unclear. In this study, we demonstrate that SDF-1α can effectively inhibit hypoxia and serum-induced apoptosis of stem cells through the mitochondrial pathway at concentrations of 0.5-2.0 μg / ml. SDF-1α inhibits the increase of mitochondrial membrane potential, inhibits the release of cytochrome c from the mitochondria to the cytoplasm, and decreases the activity of caspase 3. Our further study found that PI3K inhibitor Wortmannin and ERK1 / 2 inhibitor U0126 can counteract the effect of SDF-1α on mitochondrial pathway. The results showed that SDF-1α inhibited hypoxia and serum-induced apoptosis of stem cells through the PI3K / Akt and ERK1 / 2 signaling pathways. It is also suggested that this anti-apoptotic effect mediated by SDF-1α would also be beneficial for cell transplantation.