Basic Study
Copyright ©©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jan 26, 2022; 14(1): 104-116
Published online Jan 26, 2022. doi: 10.4252/wjsc.v14.i1.104
Therapeutic effects of menstrual blood-derived endometrial stem cells on mouse models of streptozotocin-induced type 1 diabetes
Yu-Liang Sun, Ling-Rui Shang, Rui-Hong Liu, Xin-Yi Li, Sheng-Hui Zhang, Ya-Kun Ren, Kang Fu, Hong-Bin Cheng, Badrul Hisham Yahaya, Yan-Li Liu, Jun-Tang Lin
Yu-Liang Sun, Ling-Rui Shang, Xin-Yi Li, Yan-Li Liu, Jun-Tang Lin, Stem Cell and Biotherapy Technology Research Center, Xinxiang Medical University, Xinxiang 453000, Henan Province, China
Yu-Liang Sun, Badrul Hisham Yahaya, Regenerative Medicine Cluster, Advanced Medical and Dental Institute (IPPT), Universiti Sains Malaysia, Kepala Batas 13200, Penang, Malaysia
Rui-Hong Liu, Hong-Bin Cheng, Jun-Tang Lin, College of Biomedical Engineering, Xinxiang Medical University, Xinxiang 453000, Henan Province, China
Sheng-Hui Zhang, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang Medical University, Xinxiang 453000, Henan Province, China
Ya-Kun Ren, Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang 453000, Henan Province, China
Kang Fu, Department of Technical, Henan Intercell Biotechnology co. LTD, Xinxiang 453000, Henan Province, China
Author contributions: Sun YL and Shang LR contributed equally to this work; Cheng HB, Yahaya BH, Liu YL and Lin JT conceived the idea and designed the study; Sun YL, Liu RH, Li XY, Zhang SH, Ren YK, and Fu K contributed to the literature review and integrated the materials; Sun YL and Shang LR prepared the draft; Liu YL and Lin JT revised the manuscript and approved the final version as the corresponding authors; all the authors read and approved the final manuscript.
Supported by Henan Province Foundation of China, No. 202300410307 and No. 212102310611; Xinxiang City Foundation of China, No. GG2020009.
Institutional animal care and use committee statement: The research was reviewed and approved by Xinxiang Medical University.
Conflict-of-interest statement: The author declares that there is no conflict of interest at the time of publishing this article.
Data sharing statement: No additional data is available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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: Jun-Tang Lin, PhD, Professor, Stem Cell and Biotherapy Technology Research Center, Xinxiang Medical University, East of JinSui Road, Xinxiang 453000, Henan Province, China. linjt@xxmu.edu.cn
Received: May 5, 2021
Peer-review started: May 5, 2021
First decision: June 23, 2021
Revised: July 20, 2021
Accepted: December 25, 2021
Article in press: December 25, 2021
Published online: January 26, 2022
Abstract
BACKGROUND

Type 1 diabetes (T1D), a chronic metabolic and autoimmune disease, seriously endangers human health. In recent years, mesenchymal stem cell (MSC) transplantation has become an effective treatment for diabetes. Menstrual blood-derived endometrial stem cells (MenSC), a novel MSC type derived from the decidual endometrium during menstruation, are expected to become promising seeding cells for diabetes treatment because of their noninvasive collection procedure, high proliferation rate and high immunomodulation capacity.

AIM

To comprehensively compare the effects of MenSC and umbilical cord-derived MSC (UcMSC) transplantation on T1D treatment, to further explore the potential mechanism of MSC-based therapies in T1D, and to provide support for the clinical application of MSC in diabetes treatment.

METHODS

A conventional streptozotocin-induced T1D mouse model was established, and the effects of MenSC and UcMSC transplantation on their blood glucose and serum insulin levels were detected. The morphological and functional changes in the pancreas, liver, kidney, and spleen were analyzed by routine histological and immunohistochemical examinations. Changes in the serum cytokine levels in the model mice were assessed by protein arrays. The expression of target proteins related to pancreatic regeneration and apoptosis was examined by western blot.

RESULTS

MenSC and UcMSC transplantation significantly improved the blood glucose and serum insulin levels in T1D model mice. Immunofluorescence analysis revealed that the numbers of insulin+ and CD31+ cells in the pancreas were significantly increased in MSC-treated mice compared with control mice. Subsequent western blot analysis also showed that vascular endothelial growth factor (VEGF), Bcl2, Bcl-xL and Proliferating cell nuclear antigen in pancreatic tissue was significantly upregulated in MSC-treated mice compared with control mice. Additionally, protein arrays indicated that MenSC and UcMSC transplantation significantly downregulated the serum levels of interferon γ and tumor necrosis factor α and upregulated the serum levels of interleukin-6 and VEGF in the model mice. Additionally, histological and immunohistochemical analyses revealed that MSC transplantation systematically improved the morphologies and functions of the liver, kidney, and spleen in T1D model mice.

CONCLUSION

MenSC transplantation significantly improves the symptoms in T1D model mice and exerts protective effects on their main organs. Moreover, MSC-mediated angiogenesis, antiapoptotic effects and immunomodulation likely contribute to the above improvements. Thus, MenSC are expected to become promising seeding cells for clinical diabetes treatment due to their advantages mentioned above.

Keywords: Type 1 diabetes, Menstrual blood-derived endometrial stem cell, Umbilical cord mesenchymal stem cells, Improvement, Complication

Core Tip: Mesenchymal stem cell (MSC)-based therapies have resulted in promising improvements for patients with type 1 diabetes (T1D). Menstrual blood-derived endometrial stem cells (MenSC) transplantation has therapeutic effects equal to those of umbilical cord-derived MSC, which can significantly improve the symptoms of streptozotocin-induced T1D mice and exert protective effects on their main organs; MSC-induced angiogenesis, antiapoptotic effects and immunomodulation contribute to these protective effects. The results of this study showed that MenSC are expected to become a promising alternative for clinical diabetes treatment due to their advantages, including their regular and noninvasive collection protocol, abundant availability, and superior proliferative capacity.