Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. May 26, 2025; 17(5): 105266
Published online May 26, 2025. doi: 10.4252/wjsc.v17.i5.105266
Human umbilical cord mesenchymal stem cells ameliorate liver metabolism in diabetic rats with metabolic-associated fatty liver disease
Ke-Bing Zhou, Li Nie, Mei-Li Wang, Dong-Hua Xiao, Hai-Yan Zhang, Xia Yang, Duan-Fang Liao, Xue-Feng Yang
Ke-Bing Zhou, Li Nie, Mei-Li Wang, Dong-Hua Xiao, Duan-Fang Liao, Xue-Feng Yang, Department of Gastroenterology, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, Hunan Province, China
Ke-Bing Zhou, Hai-Yan Zhang, Xia Yang, Xue-Feng Yang, Department of General Practice, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, Hunan Province, China
Xue-Feng Yang, The Clinical Research Center of Metabolic Associated Fatty Liver Disease in Hunan Province, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, Hunan Province, China
Co-first authors: Ke-Bing Zhou and Li Nie.
Co-corresponding authors: Duan-Fang Liao and Xue-Feng Yang.
Author contributions: Zhou KB, Nie L, Liao DF, and Yang XF were engaged in the design of study, animal experiments, and the drafting of manuscript. Among them, Zhou KB and Nie L made equal contributions to this work and are designated as co-first authors of this manuscript. Yang XF and Liao DF participated equally and share the corresponding authorship. Wang ML, Xiao DH, Zhang HY, and Yang X took part in the analysis of data. All the authors have read and given their approval to the final version of the manuscript.
Supported by the National Key Specialty Major Scientific Research Project of the Hunan Provincial Health Commission, No. Z2023158.
Institutional review board statement: The study was reviewed and got the approval from the Affiliated Nanhua Hospital, Hengyang Medical School, University of South China (No. 2024-KY-236).
Institutional animal care and use committee statement: This study was approved by the Institutional Animal Care and Use Committee of the Affiliated Nanhua Hospital, Hengyang Medical School, University of South China (No. 2024-KY-239).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xue-Feng Yang, PhD, Professor, Department of Gastroenterology, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, No. 336 Dongfeng South Road, Zhuhui District, Hengyang 421002, Hunan Province, China. yxf9988@126.com
Received: February 12, 2025
Revised: March 17, 2025
Accepted: May 9, 2025
Published online: May 26, 2025
Processing time: 104 Days and 1.4 Hours
Abstract
BACKGROUND

Diabetes mellitus (DM) and metabolic-associated fatty liver disease (MAFLD) are common metabolic disorders, and their coexistence can exacerbate the progression of either disease. Human umbilical cord mesenchymal stem cell (hUC-MSC) therapy has shown promising potential in the treatment of several metabolic diseases.

AIM

To investigate how hUC-MSCs affect liver metabolism in diabetic rats with MAFLD and assess their therapeutic potential and underlying mechanisms.

METHODS

A streptozotocin-induced rat model of DM with MAFLD was established, and hUC-MSCs were administered via tail vein injection. Changes in body weight, fasting blood glucose (FBG), and serum triglyceride (TG), alanine aminotransferase, aspartate aminotransferase levels, and pathological changes of liver were evaluated. Receiver operating characteristic analysis was used to assess the diagnostic value of differential metabolites and their ability to predict the therapeutic effects of hUC-MSCs. Spearman correlation was employed to analyze the relationships between liver metabolites and key biochemical markers.

RESULTS

hUC-MSC treatment significantly reduced FBG and TG levels in diabetic rats with MAFLD and improved histological steatosis and injury in the liver. Metabolomic analysis indicated that hUC-MSCs significantly ameliorated liver metabolic disturbances via their regulatory effect on several key metabolic pathways related to carbohydrate, amino acid, and lipid metabolism. Receiver operating characteristic curve analysis revealed that 70 differential metabolites had good diagnostic value for DM with MAFLD and could effectively predict the therapeutic effect of hUC-MSCs. Moreover, Spearman correlation analysis confirmed that significant correlations existed between differential liver metabolites and the concentrations of biochemical markers (FBG, TG, alanine aminotransferase, aspartate aminotransferase).

CONCLUSION

hUC-MSCs alleviate liver metabolic disturbances in diabetic rats with MAFLD, thereby mitigating the pathological state of DM and slowing the progression of MAFLD.

Keywords: Human umbilical cord mesenchymal stem cells; Diabetes mellitus; Metabolic-associated fatty liver disease; Blood glucose; Triglyceride; Liver function; Liver metabolism

Core Tip: Current treatment methods for diabetes mellitus (DM) with metabolic-associated fatty liver disease (MAFLD) remain limited, and there is an urgent need to identify novel and effective therapeutic strategies. In this study, a rat model of DM with MAFLD was established using streptozotocin, and human umbilical cord mesenchymal stem cell were administered via tail vein injection as an intervention. Our findings showed that human umbilical cord mesenchymal stem cell alleviate liver metabolic disturbances in diabetic rats with MAFLD, consequently mitigating the pathological state of DM and slowing the progression of MAFLD.