Exosomes Derived From Human Mesenchymal Stem Cells Preserve Mouse Islet Survival and Insulin Secretion Function Publisher



Keshtkar S^{1, 2} ; Kaviani M² ; Sarvestani FS² ; Ghahremani MH¹ ; Aghdaei MH² ; Alabdullah IH³ ; Azarpira N² Show Affiliations
Source: EXCLI Journal Published:2020

Abstract

Islet cell death and loss of function after isolation and before transplantation is considered a key barrier to success-ful islet transplantation outcomes. Mesenchymal stem cells (MSCs) have been used to protect isolated islets owing to their paracrine potential partially through the secretion of vascular endothelial growth factor (VEGF). The para-crine functions of MSCs are also mediated, at least in part, by the release of extracellular vesicles including exo-somes. In the present study, we examined (i) the effect of exosomes from human MSCs on the survival and function of isolated mouse islets and (ii) whether exosomes contain VEGF and the potential impact of exosomal VEGF on the survival of mouse islets. Isolated mouse islets were cultured for three days with MSC-derived exosomes (MSC-Exo), MSCs, or MSC-conditioned media without exosomes (MSC-CM-without-Exo). We investigated the effects of the exosomes, MSCs, and conditioned media on islet viability, apoptosis and function. Besides the expression of apoptotic and pro-survival genes, the production of human and mouse VEGF proteins was evaluated. The MSCs and MSC-Exo, but not the MSC-CM-without-Exo, significantly decreased the percentage of apoptotic cells and increased islet viability following the downregulation of pro-apoptotic genes and the upregulation of pro-survival factors, as well as the promotion of insulin secretion. Human VEGF was observed in the isolated exo-somes, and the gene expression and protein production of mouse VEGF significantly increased in islets cultured with MSC-Exo. MSC-derived exosomes are as efficient as parent MSCs for mitigating cell death and improving islet survival and function. This cytoprotective effect was probably mediated by VEGF transfer, suggesting a piv-otal strategy for ameliorating islet transplantation outcomes. © 2020, Leibniz Research Centre for Working Environment and Human Factors. All rights reserved.