Abstract
BackgroundTransplantation of bone marrow-derived mesenchymal stem cells (BMSCs) is one of the new therapeutic strategies for treating ischemic stroke. However, the relatively poor migratory capacity of BMSCs toward infarcted regions limited the therapeutic potential of this approach. Pharmacological preconditioning can increase the expression of CXC chemokine receptor 4 (CXCR4) in BMSCs and enhance cell migration toward the injury site. In the present study, we investigated whether tetramethylpyrazine (TMP) preconditioning could enhance BMSCs migration to the ischemic brain and improve functional recovery through upregulating CXCR4 expression.MethodsBMSCs were identified by flow cytometry analysis. BMSCs migration was evaluated in vitro by transwell migration assay, and CXCR4 expression was measured by quantitative reverse transcription-polymerase chain reaction and western blot analysis. In rats with focal cerebral ischemia, the neurological function was evaluated by the modified neurological severity score, the adhesive removal test and the corner test. The homing BMSCs and angiogenesis were detected by immunofluorescence, and expression of stromal cell-derived factor-1 (SDF-1) and CXCR4 was measured by western blot analysis.ResultsFlow cytometry analysis demonstrated that BMSCs expressed CD29 and CD90, but not CD34 and CD45. TMP pretreatment dose-dependently induced BMSCs migration and CXCR4 expression in vitro, which was significantly inhibited by AMD3100, a CXCR4 antagonist. In rat stroke models, we found more TMP-preconditioned BMSCs homing toward the infarcted regions than nonpreconditioned cells, leading to improved neurological performance and enhanced angiogenesis. Moreover, TMP-preconditioned BMSCs significantly upregulated the protein expression of SDF-1 and CXCR4 in the ischemic boundary regions. These beneficial effects of TMP preconditioning were blocked by AMD3100.ConclusionTMP preconditioning enhances the migration and homing ability of BMSCs, increases CXCR4 expression, promotes angiogenesis, and improves neurological performance. Therefore, TMP preconditioning may be an effective strategy to improve the therapeutic potency of BMSCs for ischemic stroke due to enhanced BMSCs migration to ischemic regions.
Highlights
Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) is one of the new therapeutic strategies for treating ischemic stroke
Statistical analysis Data were presented as mean ± standard deviation (SD) and were analyzed using SPSS software. modified neurological severity score (mNSS) was analyzed by Identification of BMSCs The primary BMSCs cultured in the culture dish displayed short bar shapes initially
Cotreatment of BMSCs with AMD3100 (100 μg/ml), a CXC chemokine receptor 4 (CXCR4) antagonist, significantly inhibited the effects of TMP on cell mobility (Fig. 2). These results indicated that preconditioning with TMP promoted BMSCs migration through stromal cell-derived factor-1 (SDF-1)/CXCR4 pathway
Summary
Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) is one of the new therapeutic strategies for treating ischemic stroke. Pharmacological preconditioning can increase the expression of CXC chemokine receptor 4 (CXCR4) in BMSCs and enhance cell migration toward the injury site. We investigated whether tetramethylpyrazine (TMP) preconditioning could enhance BMSCs migration to the ischemic brain and improve functional recovery through upregulating CXCR4 expression. Bone marrow-derived mesenchymal stem cells (BMSCs) represent an ideal candidate for cell transplantation therapy because they are obtained and can be expanded rapidly ex vivo [4]. BMSCs transplantation is reported to be safe and effective for the treatment of ischemic stroke [5,6,7]. Strategies promoting BMSCs migration into the peri-ischemic brain tissue may enhance the effectiveness of BMSCs-based therapy [10]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
