Wei Nie1,2, Xiaoqian Ma1,2, Cejun Yang1,2, Zeyi Chen2, Pengfei Rong1, Minghua Wu1, Jianhui Jiang3, Mengqun Tan2, Shounan Yi2,4, Wei Wang1,2. 1. Cell Transplantation and Gene Therapy Institute, The Third Xiang Ya Hospital, Central South University, Changsha, Hunan, China. 2. Engineering and Technology Research Center for Xenotransplantation of Hunan Province, Changsha, China. 3. State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, China. 4. Center for Transplant and Renal Research, Westmead Institute for Medical Research, University of Sydney, Westmead, NSW, Australia.
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.
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.
Authors: M Rezaa Mohammadi; Samuel Mathew Rodriguez; Jennifer Cam Luong; Shiri Li; Rui Cao; Hamad Alshetaiwi; Hien Lau; Hayk Davtyan; Mathew Blurton Jones; Mahtab Jafari; Kai Kessenbrock; S Armando Villalta; Paul de Vos; Weian Zhao; Jonathan R T Lakey Journal: Commun Biol Date: 2021-06-03
Authors: Susan A Safley; Melanie L Graham; Bradley P Weegman; Samuel A Einstein; Graham F Barber; Jody J Janecek; Lucas A Mutch; Amar Singh; Sabarinathan Ramachandran; Michael Garwood; Athanassios Sambanis; Klearchos K Papas; Bernhard J Hering; Collin J Weber Journal: Transplantation Date: 2020-02 Impact factor: 5.385