Human Mesenchymal Stem Cells Increases Expression of α-Tubulin and Angiopoietin 1 and 2 in Focal Cerebral Ischemia and Reperfusion

Angiogenesis is associated with improved neurologic recovery after cerebral ischemia. Human bone marrow mesenchymal stem cells (hMSCs) have been successfully used to treat ischemic stroke and were shown to induce the expression of a number of neurotrophic factors including VEGF, epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) in a rat middle cerebral artery occlusion (MCAO) ischemia model. In this study, we aimed to understand the mechanism underlying the improvement of neurological function following hMSCs transplantation into MCAO rats. We established a rat MCAO model and used immunofluorescence to evaluate alpha-tubulin expression in the hippocampus. We used RT-PCR to determine the expression of Ang-1 and Ang-2 mRNAs after transplantation of hMSCs into MCAO rats. We showed a significant decrease in alpha-tubulin expression in rats with cerebral ischemia, suggesting that alpha-tubulin is a protective protein in cerebral ischemia Transplantation of hMSCs significantly upregulated alpha-tubulin levels in the hippocampus. Transplantation of hMSCs also resulted in a significant upregulation of Ang-1 and Ang-2 mRNAs in MCAO rats. Ang-2 expression was upregulated earlier than Ang-1, suggesting that 1) transplantation of hMSCs promotes angiogenesis and that 2) Ang-2 may be an initiator of angiogenesis. Our results provide a theoretical basis for the therapeutic use of hMSCs in cerebral ischemia.