title: Human adipose-derived stem cells partially rescue the stroke syndromes by promoting spatial learning and memory in mouse middle cerebral artery occlusion model.
abstract: BACKGROUND
  Growing evidence has brought stem cell therapy to the forefront as new promising approaches towards stroke treatment. Of all candidate seeding cells, adipose-derived stem cells (ADSCs) are considered as one of the most appropriate for stroke treatment. However, previous experimental data could not reach to an agreement on the efficacy of ADSC transplantation for treating stroke in vivo as well as its mechanism which hinders their further clinical translational application.
  
  
  METHODS
  To explore their in vivo mechanism of hADSC administration on neurological injury, hADSC were labeled with Enhanced Green Fluorescence Protein expressing FG12 lentivirus and injected into MCAO mouse infarct area by in situ way. Neurological function was evaluated by Rogers Scaling System and their spatial learning and memory was determined by Morris Test. 2,3,5-triphenyltetrazolium chloride was carried out to compare the infarct area among groups. Histoimmunostaining was used to track the injected hADSCs for their in vivo migration, transdifferentiation and integration with the endogenous neuronal circuitry. To better address the underlying rescuing mechanism, qRT-PCR was performed on neural markers of MBP, MAP2, GFAP, microglia marker of Iba1.
  
  
  RESULTS
  It was found that hADSCs could promote both spatial learning and memory of MCAO mice. Co-localization of GFP and MAP2 were found in the whole cortex with significantly (P<0.01) higher percentage at the contralateral cortex compared with the ipsilateral cortex. Low percentage of GFP and GFAP co-localized cells were found at whole cortex. Meanwhile, Iba1(+) microglia and GFAP(+) astrocyte cells were significantly (P<0.05) suppressed by hADSC injection.
  
  
  CONCLUSIONS
  hADSCs could transdifferentiate into neuron like cells (MAP2(+)) in vivo and probably used as seeding cells for replacement based stem cell therapy of stroke. Also, significant immunomodulation was found. Meanwhile hADSCs could significantly protect the endogenous neuron survival. This study demonstrated that hADSC intervention with MCAO mice could apparently ameliorate stroke symptoms by direct cell replacement, enhanced immnunosuppression and increasing the viability of endogenous neurons.
authors.affiliation: Neurology Department, Shanghai Eighth People's Hospital Affiliated to Jiangsu University, Shanghai, 200233, China. feier365@163.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhou
authors.affiliation: East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. gaoshan2009@tongji.edu.cn.
authors.forename: Shane
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Pediatric Neurosurgery, Xinhua Hospital of Shanghai Jiaotong University, Shanghai, 200092, China. walozh@hotmail.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. sunrisemaomao@126.com.
authors.forename: Chenxi
authors.initials: C
authors.lastname: Sun
authors.affiliation: East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. chenlu92@icloud.com.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Tongji Hospital, Tongji University School of Medicine, Shanghai, 200442, China. ypyp68@126.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Yuan
authors.affiliation: Shanghai Xu Hui District Hospital Affiliated to Jiangsu University, Shanghai, 200031, China. zhaohaiyang15@sina.cn.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Neurology Department, Shanghai Eighth People's Hospital Affiliated to Jiangsu University, Shanghai, 200233, China. yiyi2006love@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yi
authors.affiliation: East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. qinying@tongji.edu.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Qin
authors.affiliation: East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. putishu2048@sina.com.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Dong
authors.affiliation: East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. cao20001007@163.com.
authors.forename: Limei
authors.initials: L
authors.lastname: Cao
authors.affiliation: Neurology Department, Shanghai Eighth People's Hospital Affiliated to Jiangsu University, Shanghai, 200233, China. hbpetrel@163.com.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Ren
authors.affiliation: East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. zhuliang_86@163.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Neurology Department, Shanghai Eighth People's Hospital Affiliated to Jiangsu University, Shanghai, 200233, China. sjnklq@126.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. lubingwj@hotmail.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Lu
authors.affiliation: Tongji Hospital, Tongji University School of Medicine, Shanghai, 200442, China. lab7182@tongji.edu.cn.
authors.forename: Aibin
authors.initials: A
authors.lastname: Liang
authors.affiliation: Laboratory of Clinical Visual Science, Tongji Eye Institute, Tongji University School of Medicine, Shanghai, 200092, China. gtxu@tongji.edu.cn.
authors.forename: Guo-Tong
authors.initials: GT
authors.lastname: Xu
authors.affiliation: Tianjin Hospital, Tianjin, 300211, China. hongwen_zhu@hotmail.com.|Tianjin Academy of Integrative Medicine, Tianjin, 300100, China. hongwen_zhu@hotmail.com.
authors.forename: Hongwen
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Institute of Translational Medicine, Tongji University School of Medicine, Shanghai, 200092, China. zhengliang_gao@tongji.edu.cn.|Tenth People's Hospital Affiliated to Tongji University, Shanghai, 200092, China. zhengliang_gao@tongji.edu.cn.
authors.forename: Zhengliang
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Department of Pediatric Neurosurgery, Xinhua Hospital of Shanghai Jiaotong University, Shanghai, 200092, China. majie365@hotmail.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.affiliation: East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. xunymc2000@yahoo.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Neurology Department, Shanghai Eighth People's Hospital Affiliated to Jiangsu University, Shanghai, 200233, China. cxwp65@163.com.
authors.forename: Xu
authors.initials: X
authors.lastname: Chen
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002465:Cell Movement; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000628:therapy*; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D065853:Spatial Learning; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C489788:MAP2 protein, human; D008869:Microtubule-Associated Proteins