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

被引：139
作者：
Moon, Gyeong Joon [1 ,2 ]
Sung, Ji Hee [1 ,3 ]
Kim, Dong Hee [1 ,3 ]
Kim, Eun Hee [1 ,3 ]
Cho, Yeon Hee [1 ,3 ]
Son, Jeong Pyo [1 ,4 ]
Cha, Jae Min [5 ]
Bang, Oh Young [1 ,3 ,4 ,6 ]
机构：
[1] Sungkyunkwan Univ, Sch Med, Translat & Stem Cell Res Lab Stroke, Seoul 06351, South Korea
[2] Kyungpook Natl Univ, Sch Life Sci, BK21 Plus KNU Creat BioRes Grp, Daegu 41566, South Korea
[3] Samsung Med Ctr, Stem Cell & Regenerat Med Inst Future Med, Seoul 06351, South Korea
[4] Sungkyunkwan Univ, Samsung Adv Inst Hlth Sci & Technol, Seoul 06351, South Korea
[5] Incheon Natl Univ, 3D Stem Cell Bioproc Lab, Dept Mechatron, Incheon 22012, South Korea
[6] Sungkyunkwan Univ, Sch Med, Dept Neurol, Samsung Med Ctr, Seoul 06351, South Korea
来源：
TRANSLATIONAL STROKE RESEARCH | 2019年 / 10卷 / 05期
关键词：
Stroke; Mesenchymal stem cells; Extracellular vesicles; Neurogenesis; Angiogenesis; MicroRNAs; STROMAL CELLS; PROMOTE ANGIOGENESIS; IN-VITRO; MICROVESICLES; ISCHEMIA; HYPOXIA; METAANALYSIS; PLASTICITY; FORELIMB; DELIVERY;
D O I：
10.1007/s12975-018-0668-1
中图分类号：
R74 [神经病学与精神病学];
学科分类号：
摘要：
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.
引用
收藏
页码：509 / 521
页数：13
相关论文
共 50 条
[1]   Stroke Induces Mesenchymal Stem Cell Migration to Infarcted Brain Areas Via CXCR4 and C-Met Signaling [J].
Bang, Oh Young ;
Moon, Gyeong Joon ;
Kim, Dong Hee ;
Lee, Ji Hyun ;
Kim, Sooyoon ;
Son, Jeong Pyo ;
Cho, Yeon Hee ;
Chang, Won Hyuk ;
Kim, Yun-Hee .
TRANSLATIONAL STROKE RESEARCH, 2017, 8 (05) :449-460
[2]   Adult Stem Cell Therapy for Stroke: Challenges and Progress [J].
Bang, Oh Young ;
Kim, Eun Hee ;
Cha, Jae Min ;
Moon, Gyeong Joon .
JOURNAL OF STROKE, 2016, 18 (03) :256-266
[3]   Extracellular vesicles derived from human bone marrow mesenchymal stem cells promote angiogenesis in a rat myocardial infarction model [J].
Bian, Suyan ;
Zhang, Liping ;
Duan, Liufa ;
Wang, Xi ;
Min, Ying ;
Yu, Hepeng .
JOURNAL OF MOLECULAR MEDICINE-JMM, 2014, 92 (04) :387-397
[4]   Central nervous system entry of peripherally injected umbilical cord blood cells is not required for neuroprotection in stroke [J].
Borlongan, CV ;
Hadman, M ;
Sanberg, CD ;
Sanberg, PR .
STROKE, 2004, 35 (10) :2385-2389
[5]   Efficient scalable production of therapeutic microvesicles derived from human mesenchymal stem cells [J].
Cha, Jae Min ;
Shin, Eun Kyoung ;
Sung, Ji Hee ;
Moon, Gyeong Joon ;
Kim, Eun Hee ;
Cho, Yeon Hee ;
Park, Hyung Dal ;
Bae, Hojae ;
Kim, Jinseok ;
Bang, Oh Young .
SCIENTIFIC REPORTS, 2018, 8
[6]   Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats [J].
Chen, JL ;
Li, Y ;
Wang, L ;
Zhang, ZG ;
Lu, DY ;
Lu, M ;
Chopp, M .
STROKE, 2001, 32 (04) :1005-1011
[7]   Ischemic rat brain extracts induce human marrow stromal cell growth factor production [J].
Chen, XG ;
Li, Y ;
Wang, L ;
Katakowski, M ;
Zhang, LJ ;
Chen, JL ;
Xu, YX ;
Gautam, SC ;
Chopp, M .
NEUROPATHOLOGY, 2002, 22 (04) :275-279
[8]   Enhancing trophic support of mesenchymal stem cells by ex vivo treatment with trophic factors [J].
Choi, Yun Jung ;
Li, Wen Yu ;
Moon, Gyeong Joon ;
Lee, Phil Hyu ;
Ahn, Young Hwan ;
Lee, Gwang ;
Bang, Oh Young .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 2010, 298 (1-2) :28-34
[9]   Shedding microvesicles: artefacts no more [J].
Cocucci, Emanuele ;
Racchetti, Gabriella ;
Meldolesi, Jacopo .
TRENDS IN CELL BIOLOGY, 2009, 19 (02) :43-51
[10]   Extracellular Vesicles Improve Post-Stroke Neuroregeneration and Prevent Postischemic Immunosuppression [J].
Doeppner, Thorsten R. ;
Herz, Josephine ;
Goergens, Andre ;
Schlechter, Jana ;
Ludwig, Anna-Kristin ;
Radtke, Stefan ;
de Miroschedji, Kyra ;
Horn, Peter A. ;
Giebel, Bernd ;
Hermann, Dirk M. .
STEM CELLS TRANSLATIONAL MEDICINE, 2015, 4 (10) :1131-1143
12345