Table of Contents
International Journal of Proteomics
Volume 2012 (2012), Article ID 971907, 14 pages
http://dx.doi.org/10.1155/2012/971907
Research Article

Proteolytic Potential of the MSC Exosome Proteome: Implications for an Exosome-Mediated Delivery of Therapeutic Proteasome

1Institute of Medical Biology, A*STAR, 8A Biomedical Grove, No. 06-06 Immunos, Singapore 138648
2School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551
3Laboratory of Experimental Cardiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
4The Netherlands Heart Institute, Catharijnesingel 52, 3511 GC Utrecht, The Netherlands
5Cardiovascular Research Institute, and YLL School of Medicine, NUS, Singapore 119074
6Department of Surgery, YLL School of Medicine, NUS, Singapore 119074
7Bioprocessing Technology Institute, A*STAR, Singapore 138671

Received 1 February 2012; Revised 27 March 2012; Accepted 1 June 2012

Academic Editor: John G. Marshall

Copyright © 2012 Ruenn Chai Lai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Mesenchymal stem cells (MSCs) are used in many of the current stem cell-based clinical trials and their therapeutic efficacy has increasingly been attributed to secretion of paracrine factors. We have previously demonstrated that a therapeutic constituent of this secretion is exosome, a secreted bilipid membrane vesicle of ~50–100 nm with a complex cargo that is readily internalized by H9C2 cardiomyocytes. It reduces infarct size in a mouse model of myocardial ischemia/reperfusion (MI/R) injury. We postulate that this therapeutic efficacy is derived from the synergy of a select permutation of individual exosome components. To identify protein candidates in this permutation, the proteome was profiled and here we identified 20S proteasome as a protein candidate. Mass spectrometry analysis detected all seven α and seven β chains of the 20S proteasome, and also the three beta subunits of “immunoproteasome” with a very high confidence level. We demonstrated that a functional proteasome copurified with MSC exosomes with a density of 1.10–1.18 g/mL, and its presence correlated with a modest but significant reduction in oligomerized protein in a mouse model of myocardial infarction. Circulating proteasomes in human blood also copurified with exosomes. Therefore, 20S proteasome is a candidate exosome protein that could synergize with other constituents to ameliorate tissue damage.