title: Timing and dose regimens of marrow mesenchymal stem cell transplantation affect the outcomes and neuroinflammatory response after ischemic stroke.
abstract: OBJECTIVE
  Intravenous transplantation of bone marrow mesenchymal stem cells (BMSCs) had been documented to improve functional outcome after ischemic stroke. However, the timing and appropriate cell number of transplantation to achieve better outcome after an episode of stroke remain further to be optimized.
  
  
  METHODS
  To determine the optimal conditions, we transplanted different concentrations of BMSCs at different time points in a rat model of ischemic stroke. Infarction volume and neurological behavioral tests were performed after ischemia.
  
  
  RESULTS
  We found that transplantation of BMSCs at 3 and 24 h, but not 7 days after focal ischemia, significantly reduced the lesion volume and improved motor deficits. We also found that transplanted cells at 1 × 10(6) to 10(7) , but not at 1 × 10(4) to 10(5) , significantly improved functional outcome after stroke. In addition to inhibiting macrophages/microglia activation in the ischemic brain, BMSC transplantation profoundly reduced infiltration of gamma delta T (γδT) cells, which are detrimental to the ischemic brain, and significantly increased regulatory T cells (Tregs), along with altered Treg-associated cytokines in the ischemic brain.
  
  
  CONCLUSIONS
  Our data suggest that timing and cell dose of transplantation determine the therapeutic effects after focal ischemia by modulating poststroke neuroinflammation.
authors.affiliation: Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.
authors.forename: Liu-Qing
authors.initials: LQ
authors.lastname: Wang
authors.forename: Zhen-Zhen
authors.initials: ZZ
authors.lastname: Lin
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Zhang
authors.forename: Bei
authors.initials: B
authors.lastname: Shao
authors.forename: Li
authors.initials: L
authors.lastname: Xiao
authors.forename: Hui-Gang
authors.initials: HG
authors.lastname: Jiang
authors.forename: Qi-Chuan
authors.initials: QC
authors.lastname: Zhuge
authors.forename: Luo-Kun
authors.initials: LK
authors.lastname: Xie
authors.forename: Brian
authors.initials: B
authors.lastname: Wang
authors.forename: Dong-Ming
authors.initials: DM
authors.lastname: Su
authors.forename: Kun-Lin
authors.initials: KL
authors.lastname: Jin
mesh_terms: D000328:Adult; D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology / Q000601:surgery; D002545:Brain Ischemia / Q000276:immunology* / Q000473:pathology / Q000601:surgery*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000276:immunology / Q000473:pathology / Q000601:surgery; D008264:Macrophages / Q000502:physiology; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D017628:Microglia / Q000502:physiology; D008875:Middle Aged; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D020521:Stroke / Q000276:immunology* / Q000473:pathology / Q000601:surgery*; D013601:T-Lymphocytes / Q000502:physiology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D016207:Cytokines
keywords: Injury; Ischemia; Marrow mesenchymal stem cells; Neuroinflammation; Stroke; Transplantation