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Sci Rep. 2016 Sep 9;6:33038. doi: 10.1038/srep33038.

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

Author information

1
Institute for BioMedical Convergence, Catholic Kwandong University-International St. Mary's Hospital, Incheon 22711, Republic of Korea.
2
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.
3
Department of Physiology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
4
Department of Applied Chemistry, College of Applied Science, Kyung Hee University, Yongin, 17104, Republic of Korea.
5
Department of Biomedical Sciences, Catholic Kwandong University College of Medicine, Gangneung-si, Gangwon-do 25601, Republic of Korea.

Abstract

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.

PMID:
27609711
PMCID:
PMC5016792
DOI:
10.1038/srep33038
[Indexed for MEDLINE]
Free PMC Article

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