Human mesenchymal-stem-cells-derived exosomes are important in enhancing porcine islet resistance to hypoxia

Xenotransplantation. 2018 Sep;25(5):e12405. doi: 10.1111/xen.12405. Epub 2018 Jun 22.

Abstract

Background: Hypoxia-induced damage is one of the key factors associated with islet graft dysfunction. Mesenchymal stem cells (MSCs) could be used to enhance the therapeutic effect of islet transplantation due to their paracrine potential such as exosomes. In this study, we investigated whether exosomes from human umbilical cord-derived MSC-conditioned medium (hu-MSC-CM) could increase the survival and function of neonatal porcine islet cell clusters (NICCs) exposed to hypoxia.

Methods: Neonatal porcine islet cell clusters were cultured with hu-MSC-CM, with or without exosomes, and native medium RPMI-1640 (Control) under hypoxic conditions (1% O2 ). The effects of exosomes on NICCs viability and function in vitro were examined by FACS, the Loops system, and the Extracellular Flux assay, respectively.

Results: Compared with NICCs cultured in RPMI-1640 medium and hu-MSC-CM without exosomes, the survival ratio, viability, and function increased in NICCs cultured in hu-MSC-CM with exosomes.

Conclusions: This study found that hu-MSC-CM could protect NICCs from hypoxia-induced dysfunction, and exosomes played an important role in hypoxic resistance, suggesting a potential strategy to improve islet transplantation outcomes.

Keywords: function; hypoxia; mesenchymal stem cells; neonatal porcine islet cell clusters; viability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Culture Media, Conditioned / metabolism
  • Disease Models, Animal
  • Exosomes / immunology*
  • Humans
  • Hypoxia*
  • Islets of Langerhans / cytology*
  • Islets of Langerhans Transplantation / methods
  • Mesenchymal Stem Cell Transplantation / methods
  • Mesenchymal Stem Cells / cytology*
  • Swine
  • Transplantation, Heterologous / methods

Substances

  • Culture Media, Conditioned