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Microvesicles from brain-extract-treated mesenchymal stem cells improve neurological functions in a rat model of ischemic stroke

 Ji Yong Lee  ;  Eiru Kim  ;  Seong-Mi Choi  ;  Dong-Wook Kim  ;  Kwang Pyo Kim  ;  Insuk Lee  ;  Han-Soo Kim 
 SCIENTIFIC REPORTS, Vol.6 : 33038, 2016 
Journal Title
Issue Date
Animals ; Brain* ; Brain Chemistry ; Brain Ischemia/metabolism ; Brain Ischemia/pathology ; Brain Ischemia/physiopathology ; Brain Ischemia/therapy* ; Cell-Derived Microparticles* ; Complex Mixtures/chemistry ; Complex Mixtures/pharmacology* ; Disease Models, Animal ; Male ; Mesenchymal Stromal Cells* ; Rats ; Rats, Sprague-Dawley ; Recovery of Function* ; Stroke/pathology ; Stroke/physiopathology ; Stroke/therapy*
Transplantation of mesenchymal stem cells (MSCs) was reported to improve functional outcomes in a rat model of ischemic stroke, and subsequent studies suggest that MSC-derived microvesicles (MVs) can replace the beneficial effects of MSCs. Here, we evaluated three different MSC-derived MVs, including MVs from untreated MSCs (MSC-MVs), MVs from MSCs treated with normal rat brain extract (NBE-MSC-MVs), and MVs from MSCs treated with stroke-injured rat brain extract (SBE-MSC-MVs), and tested their effects on ischemic brain injury induced by permanent middle cerebral artery occlusion (pMCAO) in rats. NBE-MSC-MVs and SBE-MSC-MVs had significantly greater efficacy than MSC-MVs for ameliorating ischemic brain injury with improved functional recovery. We found similar profiles of key signalling proteins in NBE-MSC-MVs and SBE-MSC-MVs, which account for their similar therapeutic efficacies. Immunohistochemical analyses suggest that brain-extract-treated MSC-MVs reduce inflammation, enhance angiogenesis, and increase endogenous neurogenesis in the rat brain. We performed mass spectrometry proteomic analyses and found that the total proteomes of brain-extract-treated MSC-MVs are highly enriched for known vesicular proteins. Notably, MSC-MV proteins upregulated by brain extracts tend to be modular for tissue repair pathways. We suggest that MSC-MV proteins stimulated by the brain microenvironment are paracrine effectors that enhance MSC therapy for stroke injury.
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1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Dong Wook(김동욱) ORCID logo https://orcid.org/0000-0002-5025-1532
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