Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. May 26, 2022; 14(5): 330-346
Published online May 26, 2022. doi: 10.4252/wjsc.v14.i5.330
Human amniotic fluid stem cell therapy can help regain bladder function in type 2 diabetic rats
Ching-Chung Liang, Steven W Shaw, Yung-Hsin Huang, Tsong-Hai Lee
Ching-Chung Liang, Yung-Hsin Huang, Female Urology Section, Department of Obstetrics and Gynecology, Linkou Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
Steven W Shaw, Division of Obstetrics, Department of Obstetrics and Gynecology, Taipei Chang Gung Memorial Hospital, Taipei 105, Taiwan
Steven W Shaw, Prenatal Cell and Gene Therapy Group, Institute for Women’s Health, University College London, London WC1E 6BT, United Kingdom
Tsong-Hai Lee, Stroke Center and Department of Neurology, Linkou Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
Author contributions: Liang CC and Lee TH designed the study and wrote the manuscript; Liang CC and Lee TH were responsible for obtaining funds; Liang CC, Shaw SW, and Huang YH collected the tissue samples; Liang CC, Shaw SW, and Huang YH conducted the experimental analysis; Huang YH performed all laboratory tests; and all authors read and approved the final manuscript.
Supported by the Linkou Chang Gung Memorial Hospital grants, No. CMRPG3J0951 and No. CMRPG3H1041-2; and Ministry of Science and Technology Taiwan grants, No. MOST 107-2314-B-182A-101 and No. MOST 109-2314-B-182A-084.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board at Linkou Chang Gung Memorial Hospital (No. 201701998A3).
Institutional animal care and use committee statement: The present work was approved by the Institutional Ethics Committee for the Care and Use of Experimental Animals (No. 2017121812). It was carried out in accordance with USP guidelines, ARRIVE guidelines, and the EC Directive 2010/63/EU for animal experiments (http://ec.europa.eu/environment/chemicals/Lab_animals/Legislation_en.htm).
Conflict-of-interest statement: The authors have no conflicts of interest to disclose.
Data sharing statement: No additional data are 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: Tsong-Hai Lee, PhD, Professor, Stroke Center and Department of Neurology, Linkou Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, No. 5, Fu-Hsing Street, Kweishan, Taoyuan 333, Taiwan. thlee@adm.cgmh.org.tw
Received: October 26, 2021
Peer-review started: October 26, 2021
First decision: December 4, 2021
Revised: January 3, 2022
Accepted: April 25, 2022
Article in press: April 25, 2022
Published online: May 26, 2022
Abstract
BACKGROUND

Diabetes mellitus (DM) is a serious and growing global health burden. It is estimated that 80% of diabetic patients have micturition problems such as poor emptying, urinary incontinence, urgency, and urgency incontinence. Patients with diabetic bladder dysfunction are often resistant to currently available therapies. It is necessary to develop new and effective treatment methods.

AIM

To examine the therapeutic effect of human amniotic fluid stem cells (hAFSCs) therapy on bladder dysfunction in a type 2 diabetic rat model.

METHODS

Sixty female Sprague-Dawley rats were divided into five groups: Group 1, normal-diet control (control); group 2, high-fat diet (HFD); group 3, HFD plus streptozotocin-induced DM (DM); group 4, DM plus insulin treatment (DM + insulin); group 5, DM plus hAFSCs injection via tail vein (DM + hAFSCs). Conscious cystometric studies were done at 4 and 12 wk after insulin or hAFSCs treatment to measure peak voiding pressure, voided volume, intercontraction interval, bladder capacity, and residual volume. Immunoreactivities and/or mRNA expression of muscarinic receptors, nerve growth factor (NGF), and sensory nerve markers in the bladder and insulin, MafA, and pancreatic-duodenal homeobox-1 (PDX-1) in pancreatic beta cells were studied.

RESULTS

Compared with DM rats, insulin but not hAFSCs treatment could reduce the bladder weight and improve the voided volume, intercontraction interval, bladder capacity, and residual volume (P < 0.05). However, both insulin and hAFSCs treatment could help to regain the blood glucose and bladder functions to the levels near controls (P > 0.05). The immunoreactivities and mRNA expression of M2- and M3-muscarinic receptors (M2 and M3) were increased mainly at 4 wk (P < 0.05), while the number of beta cells in islets and the immunoreactivities and/or mRNA of NGF, calcitonin gene-related peptide (CGRP), substance P, insulin, MafA, and PDX-1 were decreased in DM rats (P < 0.05). However, insulin and hAFSCs treatment could help to regain the expression of M2, M3, NGF, CGRP, substance P, MafA, and PDX-1 to near the levels of controls at 4 and/or 12 wk (P > 0.05).

CONCLUSION

Insulin but not hAFSCs therapy can recover the bladder dysfunction caused by DM; however, hAFSCs and insulin therapy can help to regain bladder function to near the levels of control.

Keywords: Amniotic fluid, Bladder dysfunction, Diabetes, Insulin, Stem cells

Core Tip: Diabetic patients with bladder dysfunction are often resistant to currently available therapies. Stem cells demonstrate the efficacy in preclinical studies of diabetic bladder dysfunction. Human amniotic fluid stem cells (hAFSCs) can be obtained from amniotic fluid, and phenotypically and genetically stable, indicating that hAFSCs can be used as a novel source of cell therapy. Here, we demonstrated that, although it is insulin but not hAFSCs therapy that can help recover the bladder dysfunction caused by diabetes mellitus (DM), both insulin and hAFSCs treatment can help to regain bladder function to near the levels of control. Our study highlights the potential of hAFSCs for cell replacement and regeneration therapy for DM.