Human umbilical cord-derived mesenchymal stem cells alleviate oxidative stress-induced islet impairment via the Nrf2/HO-1 axis

Author:

Liu Peng1,Cao Baige2,Zhou Yang3ORCID,Zhang Huina4,Wang Congrong2

Affiliation:

1. Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai 200233 , China

2. Department of Endocrinology & Metabolism, Shanghai Fourth People's Hospital, School of Medicine, Tongji University , Shanghai 200434 , China

3. Translational Medical Center for Stem Cell Therapy, Shanghai East Hospital, School of Medicine, Tongji University , Shanghai 200092 , China

4. Stem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji University , Shanghai 200065 , China

Abstract

Abstract Hyperglycaemia-induced oxidative stress may disrupt insulin secretion and β-cell survival in diabetes mellitus by overproducing reactive oxygen species. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) exhibit antioxidant properties. However, the mechanisms by which hUC-MSCs protect β-cells from high glucose-induced oxidative stress remain underexplored. In this study, we showed that intravenously injected hUC-MSCs engrafted into the injured pancreas and promoted pancreatic β-cell function in a mouse model of type 1 diabetes mellitus. The in vitro study revealed that hUC-MSCs attenuated high glucose-induced oxidative stress and prevented β-cell impairment via the Nrf2/HO-1 signalling pathway. Nrf2 knockdown partially blocked the anti-oxidative effect of hUC-MSCs, resulting in β-cell decompensation in a high-glucose environment. Overall, these findings provide novel insights into how hUC-MSCs protect β-cells from high glucose-induced oxidative stress.

Funder

National Natural Science Foundation of China

Shanghai Science and Technology Development Funds

Shanghai Fourth People's Hospital

Shanghai Key Laboratory of Diabetes Mellitus

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Genetics,Molecular Biology,General Medicine

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