Effects of Early MSC Intervention on Preventing the Streptozotocin-Induced T1DM Progression in Mice

Lanlan Zha,Pei Li,Yi Zhang,Xiangyu Meng,Xue Li,Yue Fan,Rongxiu Zheng,Yuanlin Liu,Yang Wang,Weijiang Liu,Bin Zhou

doi:10.1155/2020/5438951

Lanlan Zha, Pei Li + Show 9 more

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https://doi.org/10.1155/2020/5438951

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Abstract

Type 1 diabetes mellitus is characterized by progressive pancreatic β-cells failure and progressive autoimmunity. It is difficult to diagnose T1DM and to prevent the pancreatic β-cells destruction because of the undetectable pancreatic β-cell necrosis and abnormal autoimmunity. Here, we built streptozotocin-induced T1DM mouse model and performed MSC injection at the early stage of T1DM. We found that MSC infusion displayed enhanced effects on reducing the pathological damage and improving the survival quality. Moreover, the delivery of MSCs inhibited Th1 cell polarization and downregulated the Th1 subset ratio. The immunomodulatory mechanism of MSC was further investigated. Real-time PCR and ELISA assays demonstrated that IFN-γ expression at both mRNA and protein level in MSC infusion T1DM mice was downregulated, partially regulated by MSC-exosome-derived miR-148a-3p. Taken together, this early therapeutic strategy may improve the clinical efficacy of MSC-based therapy in T1DM.

Highlights

Diabetes mellitus (DM) and its complications have become one of the major threats to public health nowadays
MiR-148a-3p inhibits the expression of mFasl and mIFN-γ, and delays the initiation of the autoimmune and inflammatory response, contributes to preventing the Type 1 diabetes mellitus (T1DM) progression
Six-week-old mice of the Mesenchymal stem cells (MSCs) prevention group (MP) and the diabetes mellitus group (DM) underwent STZ-induced T1DM according to the following protocol

Summary

Introduction

Diabetes mellitus (DM) and its complications have become one of the major threats to public health nowadays. Both type 1 and type 2 diabetes result from progressive pancreatic β-cell failure. Type 1 diabetes mellitus (T1DM) is often diagnosed during childhood or adolescence. T1DM is thought to be caused by progressive autoimmunity [1] and associated with obesity and metabolic disorder [2]. The defective immune disorder results in the destruction of pancreatic β-cells, and patients with T1DM remain life span insulin-dependent. Early T1DM is difficult to be diagnosed in time because of the undetectable pancreatic β-cells necrosis and abnormal autoimmunity [3]. It is of great importance to balance the immune system for T1DM prevention [4]

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