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

Abstract

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 α-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 α-tubulin expression in rats with cerebral ischemia, suggesting that α-tubulin is a protective protein in cerebral ischemia Transplantation of hMSCs significantly upregulated α-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.

Hydroxysafflor Yellow A Promotes Angiogenesis via the Angiopoietin 1/ Tie-2 Signaling Pathway

“…Ang 1 not only induces endothelial sprouting [37] but it is also integral in vascular remodeling and maturation into functional blood vessels [38]. Previous studies have also demonstrated that Ang 1 promotes functional neovascularization in myocardial ischemia [39], cerebral ischemia [40,41], and hindlimb ischemia models [42]. Therefore, our results support the in vivo relevance of the effects of HSYA on angiogenesis by increasing the expression of Ang 1.…”

Human Umbilical Cord Mesenchymal Stem Cell Exosomes Enhance Angiogenesis Through the Wnt4/β-Catenin Pathway

“…The Wnt signaling pathway is critically involved in angiogenesis through the modulation of endothelial cell proliferation, migration, vascular sprouting, remodeling, and vascular system maturation [36][37][38]. Taverna et al reported that treatment with exosomes from chronic myelogenous leukemia caused an increase in endothelial cell motility accompanied by a loss of VE-cadherin and b-catenin from the endothelial cell surface [47].…”

Investigation of Epidermal Growth Factor, Tumor Necrosis Factor-alpha and Thioredoxin System in Rats Exposed to Cerebral Ischemia

“…EGF induces the phosphorylation reactions and alters the morphology of various cell lines derived from the nervous system. EGF plays a role as neurotransmitter or neurotrophic molecule (5,6).…”