The local microenvironment is essential to stem cell-based therapy for ischemic stroke,and spatiotemporal changes of the microenvironment in the pathological process provide vital clues for understanding the therapeutic mechanisms.However,relevant studies on microenvironmental changes were mainly confined in the acute phase of stroke,and long-term changes remain unclear.This study aimed to investigate the microenvironmental changes in the subacute and chronic phases of ischemic stroke after stem cell transplantation.Herein,induced pluripotent stem cells(iPSCs)and neural stem cells(NSCs)were transplanted into the ischemic brain established by middle cerebral artery occlusion surgery.Positron emission tomography imaging and neurological tests were applied to evaluate the metabolic and neurofunctional alterations of rats transplanted with stem cells.Quantitative proteomics was employed to investigate the protein expression profiles in iPSCs-transplanted brain in the subacute and chronic phases of stroke.Compared with NSCs-transplanted rats,significantly increased glucose metabolism and neurofunctional scores were observed in iPSCs-transplanted rats.Subsequent proteomic data of iPSCs-transplanted rats identified a total of 39 differentially expressed proteins in the subacute and chronic phases,which are involved in various ischemic stroke-related biological processes,including neuronal survival,axonal remodeling,antioxidative stress,and mitochondrial function restoration.Taken together,our study indicated that iPSCs have a positive therapeutic effect in ischemic stroke and emphasized the wide-ranging microenvironmental changes in the subacute and chronic phases.

Yao Chen;Fahuan Song;Mengjiao Tu;Shuang Wu;Xiao He;Hao Liu;Caiyun Xu;Kai Zhang;Yuankai Zhu;Rui Zhou;Chentao Jin;Ping Wang;Hong Zhang;Mei Tian

Department of Nuclear Medicine and Medical PET Center,The Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310009,China;Institute of Nuclear Medicine and Molecular Imaging,Zhejiang University,Hangzhou 310009,China;Key Laboratory of Medical Molecular Imaging of Zhejiang Province,Hangzhou 310009,China;Department of Radiology,Zhejiang Hospital,Hangzhou 310030,China;Department of PET Center The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310006,China;Key Laboratory for Biomedical Engineering of Ministry of Education,Zhejiang University,Hangzhou 310027,China;College of Biomedical Engineering and Instrument Science,Zhejiang University,Hangzhou 310027,China;Shanxi Medical University,Taiyuan 030001,China

医学前沿

[1]Yao Chen;Fahuan Song;Mengjiao Tu;Shuang Wu;Xiao He;Hao Liu;Caiyun Xu;Kai Zhang;Yuankai Zhu;Rui Zhou;Chentao Jin;Ping Wang;Hong Zhang;Mei Tian-.Quantitative proteomics revealed extensive microenvironmental changes after stem cell transplantation in ischemic stroke)[J].医学前沿,2022(03):429-441

neurofunctional

Quantitative,proteomics,revealed,extensive,microenvironmental,changes,after,stem,transplantation,ischemic,stroke,local,essential,therapy,spatiotemporal,pathological,provide,vital,clues,understanding,therapeutic,mechanisms,However,relevant,studies,were,mainly,confined,long,term,remain,unclear,This,study,aimed,investigate,subacute,chronic,phases,Herein,induced,pluripotent,cells,iPSCs,neural,NSCs,transplanted,into,brain,established,by,middle,cerebral,artery,occlusion,surgery,Positron,emission,tomography,imaging,neurological,tests,applied,evaluate,metabolic,alterations,rats,was,employed,expression,profiles,Compared,significantly,increased,glucose,metabolism,scores,observed,Subsequent,data,identified,total,differentially,expressed,proteins,which,involved,various,related,biological,processes,including,neuronal,survival,axonal,remodeling,antioxidative,stress,mitochondrial,restoration,Taken,together,our,indicated,that,have,positive,effect,emphasized,wide,ranging

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