Replicative senescence reduced the efficacy of human fetal bone marrow-derived mesenchymal stem cell intravenous treatment of cerebral infarction rats

doi:10.3969/j.issn.1006-7795.2015.06.007

Abstract

Abstract: Objective To compare the effect of intravascular transplantation of human bone marrow derived mesenchymal stromal cells(hMSCs), which at passage 4 and 10, on the cerebral infarct volume and behavioral improvement of cerebral ischemia rats. The therapeutic mechanisms, including reducing microglia activation and increasing neurotrophic factors will be observed. Methods The SD rats were divided into 4 groups, sham, ischemia vehicle, hMSC at passage 4 and passage 10 transplantation group. The distal middle cerebral artery occlusion(dMCAO) was applied in this study. The ischemia vehicle group received dMCAO surgery and intravascular saline injection. For the transplantation group, 1×10⁶ hMSCs were intravascularly transplanted into rats' tail vein at 1 hour after the ischemia onset. At 2 and 4 days after the ischemia onset, behavioral tests were performed. At 2 d after the ischemia onset, infarct volume was measured. At day 4, CD 68, the symbol of activated microglia, were evaluated in the core of ischemic area, meanwhile, the neurotrophic factors, such as brain-derived neurotrophic factor(BDNF) and insulin-like growth factor(IGF-1) in ipsilateral core ischemia cortex was also observed. Results Only hMSCs at passage 4 reduced infarct volume and improved the behavioral outcome of dMCAO rats significantly. At 4 days after the transplantation, the microglia activation of 4th passage hMSC group was significantly lower(P < 0.01) than that of ischemia vehicle group in the core area of ischemia cortex. At day 4, BDNF and IGF-1 in the ischemic core were higher in the group of hMSC at passage 4, than that in ischemia vehicle group. Human MSC at passage 10 did not change the neurotrophic cytokines in the core ischemia cortex. Conclusion Human MSC was transplanted at 1 h after the onset of ischemia to treat the ischemia damaged brain. The hMSC at early passage, but not late passage showed therapeutic effects, including decreasing infarct volume and increasing behavioral deficit. The underlying mechanisms of the difference may closely relate to that the ability of late passage hMSC in reducing microglia activation and increasing neurotrophic factors in ischemia core area was not as strong as the MSC at early passage.

Key words: cerebral infarction, mesenchymal stem cell, microglia, cytokine, transplantation

CLC Number:

R392.2+8

Huang Aihua, Zhang Pingping, Zhang Bin, Ma Buqing, Guan Yunqian, Zhou Yidan. Replicative senescence reduced the efficacy of human fetal bone marrow-derived mesenchymal stem cell intravenous treatment of cerebral infarction rats[J]. Journal of Capital Medical University, 2015, 36(6): 865-874.

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URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2015.06.007

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2015/V36/I6/865

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