Background: Stromal cell-derived factor-1 (SDF-1) and its cognate receptor, chemokine (C-X-C motif) receptor 4 (CXCR4), are involved in the migration of stem cells.
Aim: To test the hypothesis that mesenchymal stem cells (MSCs) with genetically modified CXCR4 can promote their own recruitment around the ischemic core.
Methods: Lentiviral vectors were used to overexpress the CXCR4-eGFP fusion protein (CXCR4/eGFP) or eGFP only (eGFP) or to introduce siRNA targeting endogenous CXCR4 (siRNA/eGFP) in rat mesenchymal stem cells (rMSCs). Rats were injected with either the transduced rMSCs or PBS as a control via the femoral vein following a left middle cerebral artery occlusion (MCAO).
Results: One week after MCAO, immunofluorescence staining revealed a significant increase in the number of eGFP-positive cells surrounding the infarct areas in the CXCR4-rMSC-treated group compared to the rMSC-treated control group. Conversely, there was a significant reduction in the number of eGFP-positive cells in the siRNA-rMSC-treated group. Moreover, there was an increase in the capillary vascular volume of the peri-infarct area, a reduction in the volume of the cerebral infarction and improved neurological function in the CXCR4-rMSC-treated group compared to those in the rMSC-, siRNA-rMSC- or PBS-treated groups.
Conclusion: CXCR4 overexpression in the rMSCs promoted their mobilization and enhanced neuroprotection in a rat cerebral ischemia model. This strategy may be a useful therapeutic approach for treating ischemic stroke.
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