Stem Cells and Development
Stem Cells and Development
5 years ago

The CXCR4 antagonist AMD3100 promotes mesenchymal stem cell mobilization in rats preconditioned with the hypoxia-mimicking agent cobalt chloride.

Yulin Xu, Qin Yu, Lizhen Liu, He Huang, Yongxian Hu, Limengmeng Wang, Shan Fu, Kaimin Hu, Xiaohong Yu, Binsheng Wang
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 (HIF-1α) is essential for MSC mobilization. In the present study, the effect of the hypoxia mimicking agent CoCl2 was examined on MSC mobilization. The results indicated that the frequency of circulating MSCs increased slightly by administration of CoCl2. 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 CoCl2. The frequency of colony-forming unit fibroblast (CFU-Fs) and the proportion of CD45-CD90+ 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 CoCl2 could not stimulate the release of MSCs. However, AMD3100 dramatically increased MSC mobilization efficiency in rats pretreated with CoCl2. Furthermore, we identified and compared the multi-lineage differentiation capacities of MSCs derived from BM (BM-MSCs) and mobilized PB (PB-MSCs). The results indicated that PB-MSCs exhibited higher osteogenic potential and lower adipogenic differentiation compared with BM-MSCs. The findings may inform studies investigating mechanisms of the regulation of MSC mobilization and can aid the development of clinically useful therapeutic agents.

Publisher URL: http://doi.org/10.1089/scd.2017.0191

DOI: 10.1089/scd.2017.0191

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