Human umbilical cord mesenchymal stem cells repair islet structure and function in diabetic rats through metabolic reprogramming

doi:10.4252/wjsc.122760

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World Journal of Stem Cells

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1948-0210

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Stem Cells. Oct 26, 2026; 18(10): 122760
Published online Oct 26, 2026. doi: 10.4252/wjsc.122760

Human umbilical cord mesenchymal stem cells repair islet structure and function in diabetic rats through metabolic reprogramming

Jian Xu, Xia Yang, Hai-Yan Zhang, Li-Li Wang, Yuan-Dong Luo, Shuo-Liang Yang, Ya-Jing Zhou, Ying Liu, Xue-Feng Yang

Jian Xu, Ying Liu, Department of Gastroenterology, The Second People’s Hospital of Xiangtan City, Xiangtan 411100, Hunan Province, China

Xia Yang, Hai-Yan Zhang, Li-Li Wang, Yuan-Dong Luo, Xue-Feng Yang, Department of General Practice, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, Hunan Province, China

Shuo-Liang Yang, Ya-Jing Zhou, Xue-Feng Yang, Department of Gastroenterology, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, Hunan Province, China

Co-first authors: Jian Xu and Xia Yang.

Co-corresponding authors: Ying Liu and Xue-Feng Yang.

Author contributions: Xu J, Yang X, Liu Y, and Yang XF participated in experimental design, animal experiments, and paper writing; Xu J and Yang X made equal contributions to the study and were listed as co-first authors. Liu Y and Yang XF contributed equally and served as corresponding authors. Zhang HY, Wang LL, Luo YD, Yang SL, and Zhou YJ were involved in data analysis. All authors have read and approved the final version of the manuscript.

AI contribution statement: Portions of this manuscript were edited using AI tools solely for language refinement. The authors carefully reviewed and verified all AI-assisted outputs and take full responsibility for the scientific content of the manuscript.

Supported by the Hunan Provincial Natural Science Foundation, No. 2026JJ81776, No. 2026JJ80142, and No. 2026JJ81116; and 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 approved by the Affiliated Nanhua Hospital, Hengyang Medical School, University of South China (Approval 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 Hunan Evidence-Based Biotechnology Co. Ltd. (Research Collaborating Institution of the Affiliated Nanhua Hospital, Hengyang Medical School, University of South China) (Approval No. 2024-XZSW-240301).

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 is available.

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: April 28, 2026
Revised: July 27, 2026
Accepted: October 8, 2026
Published online: October 26, 2026
Processing time: 182 Days and 4 Hours

Abstract

BACKGROUND

Diabetes mellitus (DM) is a widespread metabolic disorder primarily characterized by persistent hyperglycemia and impaired pancreatic islet function. Human umbilical cord mesenchymal stem cells (hUC-MSCs) represent a promising venue for DM treatment owing to their capacity to modulate metabolism and facilitate tissue repair.

AIM

To investigate the therapeutic effect of hUC-MSCs in DM model rats and the underlying mechanism.

METHODS

Streptozotocin was used to induce DM in Sprague-Dawley rats, and hUC-MSCs were administered interventional therapy. We then combined classic physiological and biochemical indices [such as body weight, fasting blood glucose (FBG), glycated hemoglobin (GHb), glycated serum protein (GSP), fasting insulin (FINS), and C-peptide, along with the homeostasis model assessment of insulin resistance (HOMA-IR)], histopathological evaluations [including hematoxylin and eosin (HE), TUNEL staining, and immunohistochemistry], and untargeted metabolomics to screen for key differential metabolites (KDMs) in the pancreas.

RESULTS

Treatment with hUC-MSCs significantly reduced the levels of FBG, GHb, GSP, and HOMA-IR and increased the levels of FINS and C-peptide in DM rats. HE staining showed that hUC-MSCs effectively improved islet structure by restoring the area and number of islets and reducing the cellular apoptosis rate in the pancreatic tissue. Immunohistochemical staining showed that hUC-MSCs significantly increased the number of insulin-positive β cells. Metabolomic analysis showed that hUC-MSCs improved pancreatic metabolism of DM rats by modulating various metabolic processes, such as those involved in lipid and amino acid metabolism. Receiver operating characteristic curve analysis showed that all 30 KDMs had excellent diagnostic performance, suggesting that KDMs are potential DM diagnostic biomarkers and predictors of the treatment efficacy of the hUC-MSCs. Spearman analysis showed significant correlation of KDMs with FBG, insulin, and HOMA-IR.

CONCLUSION

hUC-MSC therapy lowers blood glucose levels and enhances both the structure and functionality of islets in diabetic rats, while also supporting improvements in impaired pancreatic metabolism. Treatment with hUC-MSCs improves pancreatic metabolic disorders in the DM rats by modulating 30 KDMs.

Keywords: Human umbilical cord mesenchymal stem cells; Diabetes mellitus; Sprague-Dawley; Islet function; Pancreatic metabolomics

Core Tip: Diabetes mellitus (DM) is a prevalent metabolic disease. This study investigated the treatment efficacy of the human umbilical cord mesenchymal stem cells (hUC-MSCs) in repairing diabetic rat islets and the potential underlying mechanisms. Results showed that hUC-MSCs lowered blood glucose, improved insulin secretion and islet structure, and regulated pancreatic lipid and amino acid metabolism. Thirty key differential metabolites were identified as potential diagnostic and treatment efficacy prediction biomarkers. The results indicate that hUC-MSCs protects islets and improves glucose metabolism in DM by regulating pancreatic metabolism.