1 Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, People's Republic of China .
2 College of Life Science, Zhejiang Chinese Medical University , Hangzhou, People's Republic of China .
Stem Cells Dev. 2018 Apr 1;27(7):466-478. doi: 10.1089/scd.2017.0191. Epub 2018 Mar 13.
Mobilization of mesenchymal stem cells (MSCs) is an attractive strategy for cell therapy. Our previous study demonstrated that MSCs can be mobilized in circulating blood by short-term hypoxia, and hypoxia-inducible factor-1α is essential for MSC mobilization. In the present study, the effect of the hypoxia-mimicking agent CoCl was examined on MSC mobilization. The results indicated that the frequency of circulating MSCs increased slightly by administration of CoCl. However, the mobilization efficiency was low. Considering the critical role of stromal cell-derived factor-1α (SDF-1)/CXCR4 axis in the regulation of MSC migration, the effects of granulocyte colony-stimulating factor (G-CSF) and the CXCR4 antagonist AMD3100 were investigated on MSC mobilization. The experiments were notably demonstrated in animals preconditioned with CoCl. The frequency of colony-forming unit fibroblast and the proportion of CD45CD90 cells did not significantly increase in the peripheral blood of rats treated with G-CSF and/or AMD3100 alone. The concomitant administration of G-CSF with CoCl could not stimulate the release of MSCs. However, AMD3100 dramatically increased MSC mobilization efficiency in rats pretreated with CoCl Furthermore, we identified and compared the multilineage differentiation capacities of MSCs derived from bone marrow (BM-MSCs) and mobilized peripheral blood (PB-MSCs). The results indicated that PB-MSCs exhibited higher osteogenic potential and lower adipogenic differentiation as compared with BM-MSCs. The findings may inform studies investigating mechanisms of the regulation of MSC mobilization and can aid in the development of clinically useful therapeutic agents.
动员间充质干细胞（MSCs）是细胞治疗的一种有吸引力的策略。我们之前的研究表明，MSCs 可以通过短期缺氧在循环血液中动员，缺氧诱导因子-1α 对于 MSC 动员是必不可少的。在本研究中，检查了缺氧模拟剂 CoCl 对 MSC 动员的影响。结果表明，CoCl 给药后循环 MSC 的频率略有增加。然而，动员效率较低。考虑到基质细胞衍生因子-1α（SDF-1）/CXCR4 轴在调节 MSC 迁移中的关键作用，研究了粒细胞集落刺激因子（G-CSF）和 CXCR4 拮抗剂 AMD3100 对 MSC 动员的影响。这些实验在先用 CoCl 预处理的动物中进行了特别演示。单独用 G-CSF 和/或 AMD3100 处理的大鼠外周血中集落形成单位成纤维细胞的频率和 CD45CD90 细胞的比例没有显著增加。G-CSF 与 CoCl 同时给药不能刺激 MSC 的释放。然而，AMD3100 显著增加了用 CoCl 预处理的大鼠中 MSC 动员的效率。此外，我们鉴定并比较了源自骨髓（BM-MSCs）和动员外周血（PB-MSCs）的 MSC 的多谱系分化能力。结果表明，与 BM-MSCs 相比，PB-MSCs 具有更高的成骨潜力和更低的成脂分化能力。这些发现可能为研究 MSC 动员调节的机制提供信息，并有助于开发临床有用的治疗剂。
