期刊
CELL ADHESION & MIGRATION
卷 10, 期 4, 页码 342-359出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/19336918.2016.1139287
关键词
cell migration; chemokine receptor type 4; hypoxia; inflammation; mesenchymal stem cells; stromal cell-derived factor-1
类别
资金
- National Natural Science Foundation of China [81530050, 81500853, 81471791]
- Program for Changjiang Scholars and Innovative Research Team in University [IRT13051]
- Program for New Century Excellent Talents in University [NCET-12-1005]
Directing cell trafficking toward a target site of interest is critical for advancing stem cell therapy in clinical theranostic applications. In this study, we investigated the effects of inflammatory and/or hypoxic stimuli on the migration of bone marrow mesenchymal stem cells (BMMSCs) during in vitro culture and after in vivo implantation. Using tablet scratch experiments and observations from a transwell system, we found that both inflammatory and hypoxic stimuli significantly enhanced cell migration. However, the combination of inflammatory and hypoxic stimuli did not result in a synergistic effect. The presence of stromal cell-derived factor-1 (SDF-1) significantly enhanced cell migration irrespective of the incubation conditions, and these positive effects could be blocked by treatment with AMD3100. Based on a time course experiment, we found that preconditioning cells with either inflammatory or hypoxic stimuli for 24h or with both stimuli for 12h led to high levels of chemokine receptor type 4 (CXCR4) expression. In vivo studies further demonstrated that pretreatment of BMMSCs with inflammatory and/or hypoxic stimuli resulted in an increased number of systemically injected cells migrating toward skin injuries, and local SDF-1 administration significantly increased cell migration. These findings suggest that in vitro control of either inflammatory or hypoxic stimuli has significant potential to enhance SDF-1-directed BMMSC migration via the upregulation of CXCR4 expression. Although combining the stimuli did not necessarily lead to a synergistic effect, the potential to reduce the dose and time required for cell preconditioning indicates that combinations of various strategies warrant further exploration.
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