Exosomes derived from human mesenchymal stem cells preserve mouse islet survival and insulin secretion function

Authors

  • Somayeh Keshtkar Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  • Maryam Kaviani Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  • Fatemeh Sabet Sarvestani Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  • Mohammad Hossein Ghahremani Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  • Mahdokht Hossein Aghdaei Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  • Ismail H. Al-Abdullah Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, CA/USA
  • Negar Azarpira Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran, Telephone number: +98-71-36281529, Fax: +98-711-6473954; E-mail: negarazarpira@gmail.com https://orcid.org/0000-0002-5549-0057

DOI:

https://doi.org/10.17179/excli2020-2451

Keywords:

mesenchymal stem cell, exosome, islet, viability, function, VEGF

Abstract

Islet cell death and loss of function after isolation and before transplantation is considered a key barrier to successful 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 paracrine functions of MSCs are also mediated, at least in part, by the release of extracellular vesicles including exosomes. 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 exosomes, 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 pivotal strategy for ameliorating islet transplantation outcomes.

Published

2020-08-03

How to Cite

Keshtkar, S., Kaviani, M., Sarvestani, F. S., Ghahremani, M. H., Aghdaei, M. H., Al-Abdullah, I. H., & Azarpira, N. (2020). Exosomes derived from human mesenchymal stem cells preserve mouse islet survival and insulin secretion function. EXCLI Journal, 19, 1064–1080. https://doi.org/10.17179/excli2020-2451

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Section

Original articles

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