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ISSN: 2157-7633

Journal of Stem Cell Research & Therapy
Open Access

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Research Article

Efficiency of Exosome Production Correlates Inversely with the Developmental Maturity of MSC Donor

Tian Sheng Chen1,8*, Ronne Wee Yeh Yeo1,2, Fatih Arslan3, Yijun Yin1, Soon Sim Tan1, Ruenn Chai Lai1, Andre Choo4, Jayanthi Padmanabhan4, Chuen Neng Lee5, Dominique PV de Kleijn3,6, Kok Hian Tan7 and Sai Kiang Lim1,5*

1Institute of Medical Biology, A*STAR, 8A Biomedical Grove, 138648 Singapore

2National University of Singapore, Graduate School for Integrative Sciences and Engineering, 28 Medical Drive, 117456 Singapore

3Laboratory of Experimental Cardiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands

4Bioprocessing Technology Institute, A*STAR, 20 Biopolis Way, 138671 Singapore

5Department of Surgery, YLL School of Medicine, NUS, 5 Lower Kent Ridge Road, 119074 Singapore

6Interuniversity Cardiology Institute of the Netherlands, Catharijnesingel 52, 3511 GC Utrecht, the Netherlands

7Department of Maternal Fetal Medicine, KK Women’s and Children’s Hospital, 100 Bukit Timah Road, 229899 Singapore

8Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, College of Fisheries, Huazhong Agricultural University, Wuhan, Hubei, 430070, People’s Republic of China

*Corresponding Author:
Tian Sheng Chen
Key Laboratory of Agricultural Animal Genetics
Breeding and Reproduction of Ministry of Education
Key Laboratory of Freshwater Animal Breeding
Ministry of Agriculture, College of Fisheries
Huazhong Agricultural University
No.1, Shizishan Street, Hongshan District
Wuhan, Hubei, 430070, People’s Republic of China
Tel: +86-27-87162618
Fax: +86-27-87282113
E-mail: [email protected]
 
Sai-Kiang Lim
Research Director, A*STAR Institute of Medical Biology
Singapore, DID: +65 6407 0161
Tel: +65 6407 0150
Fax: +65 6464 2048
E-mail: [email protected]

Received date: July 18, 2013; Accepted date: August 16, 2013; Published date: August 19, 2013

Citation: Chen TS, Yeo RWY, Arslan F, Yin Y, Tan SS, et al. (2013) Efficiency of Exosome Production Correlates Inversely with the Developmental Maturity of MSC Donor. J Stem Cell Res Ther 3:145. doi:10.4172/2157-7633.1000145

Copyright: © 2013 Chen TS, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

 

Abstract

Mesenchymal stem cells (MSCs) derived from human embryonic stem cells (ESCs) and fetal tissues have been shown to secrete cardioprotective exosome, a protein- and RNA40 containing vesicle. Since the therapeutic efficacy of MSCs is inversely correlated with developmental stage of the donor, we determine if this correlation extended to the cardioprotective MSC exosomes by examining exosomes secreted by MSCs derived from non-embryonic/fetal tissues e.g. umbilical cord. Unlike ESC- and fetal-MSCs, cord-MSCs have a much smaller proliferative capacity. To circumvent this and produce sufficient MSC exosomes for testing, they were immortalized via MYC over-expression. Like ESC-MSCs, MYC immortalization of cord MSCs expanded their proliferative capacity to bypass senescence, reduced plastic adherence, enhanced growth rate, and eliminated in vitro adipogenic differentiation potential without compromising exosome production. Exosomes produced by immortalized cord-MSCs were cardioprotective, and were equally efficacious in reducing infarct size in a mouse model of myocardial ischemia/reperfusion injury. However, cord MSCs produced the least amount of exosomes followed by fetal- and then ESC-MSC in decreasing order of developmental maturity or youth of the donor tissues, suggesting that the inverse correlation between the therapeutic efficacy of MSC and developmental stage of the donor is underpinned by rate of exosome production.

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