Preconditioning of bone marrow-derived mesenchymal stromal cells by tetramethylpyrazine enhances cell migration and improves functional recovery after focal cerebral ischemia in ratsReportar como inadecuado




Preconditioning of bone marrow-derived mesenchymal stromal cells by tetramethylpyrazine enhances cell migration and improves functional recovery after focal cerebral ischemia in rats - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Stem Cell Research and Therapy

, 8:112

First Online: 12 May 2017Received: 15 November 2016Revised: 23 March 2017Accepted: 26 April 2017DOI: 10.1186-s13287-017-0565-7

Cite this article as: Li, L., Chu, L., Fang, Y. et al. Stem Cell Res Ther 2017 8: 112. doi:10.1186-s13287-017-0565-7

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.

KeywordsBone marrow-derived mesenchymal stem cells Tetramethylpyrazine Preconditioning Migration CXCR4 AbbreviationsBMSCsBone marrow-derived mesenchymal stem cells

BrdU5-Bromo-2-deoxyuridine

BSABovine serum albumin

CXCR4CXC chemokine receptor 4

DMEMDulbecco-s modified Eagle-s medium

ECAExternal carotid artery

FBSFetal bovine serum

GAPDHGlyceraldehyde-3-phosphate dehydrogenase

ICAInternal carotid artery

MCAOMiddle cerebral artery occlusion

mNSSModified neurological severity score

MSCsMesenchymal stem cells

PBSPhosphate-buffered saline

qRT-PCRQuantitative reverse transcription-polymerase chain reaction

SDStandard deviation

SDF-1Stromal cell-derived factor-1

TMPTetramethylpyrazine

vWFVon Willebrand factor





Autor: Lin Li - Lisheng Chu - Yan Fang - Yan Yang - Tiebing Qu - Jianping Zhang - Yuanjun Yin - Jingjing Gu

Fuente: https://link.springer.com/







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