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Hypoxic preconditioning improves the survival and neural effects of transplanted mesenchymal stem cells via CXCL12/CXCR4 signalling in a rat model of cerebral infarction

Yueqiang Hu,Wei Chen,Lin Wu,Lingfei Jiang,Hongling Qin,N. Tang

Published 2019 in Cell Biochemistry and Function

ABSTRACT

The treatment of neural deficiency after cerebral infarction is challenging, with limited therapeutic options. The transplantation of mesenchymal stem cells (MSCs) to the ischemic penumbra is a potential therapeutic approach. In the present study, a cerebral infarction model was generated by performing middle cerebral artery occlusion (MCAO) in SD rats. The expression of CXCR4 increased, and the number of MSCs migrating to the peri‐infarct area was higher in rats transplanted with preconditioned MSCs than in rats transplanted with untreated MSCs. The rate of apoptosis, as evaluated by TUNEL staining and immunoblotting assays, was reduced in rats receiving preconditioned MSCs. A significant amelioration of neural regeneration and improved neurological function were observed in rats injected with preconditioned MSCs compared with those injected with untreated MSCs. However, the application of an siRNA targeting CXCL12 significantly inhibited the protective role of preconditioned MSCs against apoptosis and promoted the migration of MSCs to the ischemic area, leading to impaired neuronal regeneration and limited recovery of neuronal function. Hypoxic preconditioning of MSCs prior to transplantation suppressed apoptosis and increased their migration abilities, leading to the promotion of neuronal regeneration and improvement in neural function after transplantation. This preconditioning strategy may be considered as a potential approach for the modification of MSCs prior to cell transplantation therapy in patients with cerebral infarction.

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