Skip to main content
Top
Published in: Translational Stroke Research 5/2019

01-10-2019 | Original Article

Application of Mesenchymal Stem Cell-Derived Extracellular Vesicles for Stroke: Biodistribution and MicroRNA Study

Authors: Gyeong Joon Moon, Ji Hee Sung, Dong Hee Kim, Eun Hee Kim, Yeon Hee Cho, Jeong Pyo Son, Jae Min Cha, Oh Young Bang

Published in: Translational Stroke Research | Issue 5/2019

Login to get access

Abstract

Mesenchymal stem cells (MSCs) exert their therapeutic capability through a variety of bioactive substances, including trophic factors, microRNAs, and extracellular vesicles (EVs) in infarcted tissues. We therefore hypothesized that MSC-derived EVs (MSC-EVs) possess therapeutic molecules similar to MSCs. Moreover, given their nature as nanosized and lipid-shielded particles, the intravenous infusion of MSC-EVs would be advantageous over MSCs as a safer therapeutic approach. In this study, we investigated the biodistribution, therapeutic efficacy, and mode of action of MSC-EVs in a rat stroke model. MSC-EVs successfully stimulated neurogenesis and angiogenesis in vivo. When compared to the MSC-treated group, rats treated with MSC-EVs exhibited greater behavioral improvements than the control group (p < 0.05). Our biodistribution study using fluorescence-labeled MSC-EVs and MSCs demonstrated that the amounts of MSC-EVs in the infarcted hemisphere increased in a dose-dependent manner, and were rarely found in the lung and liver. In addition, MSC-EVs were highly inclusive of various proteins and microRNAs (miRNAs) associated with neurogenesis and/or angiogenesis compared to fibro-EVs. We further analyzed those miRNAs and found that miRNA-184 and miRNA-210 were essential for promoting neurogenesis and angiogenesis of MSC-EVs, respectively. MSC-EVs represent an ideal alternative to MSCs for stroke treatment, with similar medicinal capacity but an improved safety profile that overcomes cell-associated limitations in stem cell therapy.
Appendix
Available only for authorised users
Literature
5.
go back to reference Chen J, Li Y, Wang L, Zhang Z, Lu D, Lu M, et al. Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke. 2001;32(4):1005–11.CrossRefPubMed Chen J, Li Y, Wang L, Zhang Z, Lu D, Lu M, et al. Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke. 2001;32(4):1005–11.CrossRefPubMed
13.
go back to reference Li WY, Choi YJ, Lee PH, Huh K, Kang YM, Kim HS, et al. Mesenchymal stem cells for ischemic stroke: changes in effects after ex vivo culturing. Cell Transplant. 2008;17(9):1045–59.CrossRefPubMed Li WY, Choi YJ, Lee PH, Huh K, Kang YM, Kim HS, et al. Mesenchymal stem cells for ischemic stroke: changes in effects after ex vivo culturing. Cell Transplant. 2008;17(9):1045–59.CrossRefPubMed
20.
go back to reference Schallert T, Fleming SM, Leasure JL, Tillerson JL, Bland ST. CNS plasticity and assessment of forelimb sensorimotor outcome in unilateral rat models of stroke, cortical ablation, parkinsonism and spinal cord injury. Neuropharmacology. 2000;39(5):777–87.CrossRefPubMed Schallert T, Fleming SM, Leasure JL, Tillerson JL, Bland ST. CNS plasticity and assessment of forelimb sensorimotor outcome in unilateral rat models of stroke, cortical ablation, parkinsonism and spinal cord injury. Neuropharmacology. 2000;39(5):777–87.CrossRefPubMed
21.
go back to reference Metz GA, Whishaw IQ. Cortical and subcortical lesions impair skilled walking in the ladder rung walking test: a new task to evaluate fore- and hindlimb stepping, placing, and co-ordination. J Neurosci Methods. 2002;115(2):169–79.CrossRef Metz GA, Whishaw IQ. Cortical and subcortical lesions impair skilled walking in the ladder rung walking test: a new task to evaluate fore- and hindlimb stepping, placing, and co-ordination. J Neurosci Methods. 2002;115(2):169–79.CrossRef
28.
go back to reference Chen X, Li Y, Wang L, Katakowski M, Zhang L, Chen J, et al. Ischemic rat brain extracts induce human marrow stromal cell growth factor production. Neuropathology. 2002;22(4):275–9.CrossRefPubMed Chen X, Li Y, Wang L, Katakowski M, Zhang L, Chen J, et al. Ischemic rat brain extracts induce human marrow stromal cell growth factor production. Neuropathology. 2002;22(4):275–9.CrossRefPubMed
48.
go back to reference Ratajczak MZ, Kucia M, Jadczyk T, Greco NJ, Wojakowski W, Tendera M, et al. Pivotal role of paracrine effects in stem cell therapies in regenerative medicine: can we translate stem cell-secreted paracrine factors and microvesicles into better therapeutic strategies? Leukemia. 2012;26(6):1166–73. https://doi.org/10.1038/leu.2011.389.CrossRefPubMed Ratajczak MZ, Kucia M, Jadczyk T, Greco NJ, Wojakowski W, Tendera M, et al. Pivotal role of paracrine effects in stem cell therapies in regenerative medicine: can we translate stem cell-secreted paracrine factors and microvesicles into better therapeutic strategies? Leukemia. 2012;26(6):1166–73. https://​doi.​org/​10.​1038/​leu.​2011.​389.CrossRefPubMed
Metadata
Title
Application of Mesenchymal Stem Cell-Derived Extracellular Vesicles for Stroke: Biodistribution and MicroRNA Study
Authors
Gyeong Joon Moon
Ji Hee Sung
Dong Hee Kim
Eun Hee Kim
Yeon Hee Cho
Jeong Pyo Son
Jae Min Cha
Oh Young Bang
Publication date
01-10-2019
Publisher
Springer US
Published in
Translational Stroke Research / Issue 5/2019
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI
https://doi.org/10.1007/s12975-018-0668-1

Other articles of this Issue 5/2019

Translational Stroke Research 5/2019 Go to the issue