title: Proteolytic Potential of the MSC Exosome Proteome: Implications for an Exosome-Mediated Delivery of Therapeutic Proteasome.
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.
authors.affiliation: Institute of Medical Biology, A∗STAR, 8A Biomedical Grove, No. 06-06 Immunos, Singapore 138648.
authors.forename: Ruenn Chai
authors.initials: RC
authors.lastname: Lai
authors.forename: Soon Sim
authors.initials: SS
authors.lastname: Tan
authors.forename: Bao Ju
authors.initials: BJ
authors.lastname: Teh
authors.forename: Siu Kwan
authors.initials: SK
authors.lastname: Sze
authors.forename: Fatih
authors.initials: F
authors.lastname: Arslan
authors.forename: Dominique P
authors.initials: DP
authors.lastname: de Kleijn
authors.forename: Andre
authors.initials: A
authors.lastname: Choo
authors.forename: Sai Kiang
authors.initials: SK
authors.lastname: Lim