Amniotic Membrane Extract Protects Islets From Serum-Deprivation Induced Impairments and Improves Islet Transplantation Outcome.

Zhaoming Yang,Chengshuo Zhang,Jianzhen Lin,Jialin Zhang,Feng Li,Xiaohang Li,Tingwei Guo,Ning Sun

doi:10.3389/fendo.2020.587450

Abstract

Islet culture prior to transplantation is a standard practice in many transplantation centers. Nevertheless, the abundant islet mass loss and function impairment during this serum-deprivation culture period restrain the success of islet transplantation. In the present study, we used a natural biomaterial derived product, amniotic membrane extract (AME), as medium supplementation of islet pretransplant cultivation to investigate its protective effect on islet survival and function and its underlying mechanisms, as well as the engraftment outcome of islets following AME treatment. Results showed that AME supplementation improved islet viability and function, and decreased islet apoptosis and islet loss during serum-deprived culture. This was associated with the increased phosphorylation of PI3K/Akt and MAPK/ERK signaling pathway. Moreover, transplantation of serum-deprivation stressed islets that were pre-treated with AME into diabetic mice revealed better blood glucose control and improved islet graft survival. In conclusion, AME could improve islet survival and function in vivo and in vitro, and was at least partially through increasing phosphorylation of PI3K/Akt and MAPK/ERK signaling pathway.

Highlights

Islet transplantation is an effective b-cell replacement therapy that could help type 1 diabetes mellitus (T1DM) patients to achieve euglycemia [1]
In order to investigate whether amniotic membrane extract (AME) affects the viability of serum-deprived islets, 0.1–1.5 mg/ml AME were applied to islet culture media
Results showed that AME supplementation significantly increased the expression of Bcl2 compared to serum-deprivation group (p < 0.001), while there was no significant difference in the expression of Bax between AME and serum-deprivation group

Summary

Introduction

Islet transplantation is an effective b-cell replacement therapy that could help type 1 diabetes mellitus (T1DM) patients to achieve euglycemia [1]. Islet culture is not included in the Edmonton Protocol, which required isolated islets to be infused within 4 h [2, 7]. This causes some difficulties in recipient preparation and islet quality control, and increases the risk of operation. In clinical islet transplantation, human serum albumin (HSA) is used as a supplementation of the culture media [17] instead of FBS to avoid animal-derived factors, which causes a serum-deprived condition that may impair islet viability and function [18, 19]. It’s urgent to explore strategies to prevent islet apoptosis during serum-deprived cultivation in vitro

Methods

Results

Conclusion