Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. May 26, 2020; 12(5): 368-380
Published online May 26, 2020. doi: 10.4252/wjsc.v12.i5.368
Safety of menstrual blood-derived stromal cell transplantation in treatment of intrauterine adhesion
Qi-Yuan Chang, Si-Wen Zhang, Ping-Ping Li, Zheng-Wei Yuan, Ji-Chun Tan
Qi-Yuan Chang, Si-Wen Zhang, Ping-Ping Li, Ji-Chun Tan, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
Qi-Yuan Chang, Si-Wen Zhang, Ping-Ping Li, Ji-Chun Tan, Key Laboratory of Reproductive Dysfunction Diseases and Fertility Remodeling of Liaoning Province, Shenyang 110004, Liaoning Province, China
Zheng-Wei Yuan, Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital of China Medical University, Benxi 117004, Liaoning Province, China
Author contributions: Chang QY was responsible for the experiment design and conception and data collection; Zhang SW was responsible for experiment design and data analysis; Li PP was responsible for the experiment design and manuscript revision; Yuan ZW provided the technical guidance; Tan JC designed the work, provided the technical guidance, and approved the final version of the manuscript; Chang QY, Zhang SW, and Li PP wrote the manuscript; all authors read and approved the final manuscript.
Supported by the National Key Research and Development Program, No. 2018YFC1002105; the Key Research and Development Program of Liaoning Province, No. 2018020222; and the Major Special Construction Plan for Discipline Construction Project of China Medical University, No. 3110118033.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of the Shengjing Hospital affiliated to China Medical University (2017PS330K).
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care of Shengjing Hospital Affiliated to China Medical University and were conducted in accordance with the AAALAC and IACUC guidelines.
Conflict-of-interest statement: The authors declare that they have no competing interests.
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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Ji-Chun Tan, PhD, Professor, Doctor, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 39, Huaxiang Road, Tiexi District, Shenyang 110022, Liaoning Province, China. tjczjh@163.com
Received: February 24, 2020
Peer-review started: February 24, 2020
First decision: March 28, 2020
Revised: April 3, 2020
Accepted: April 23, 2020
Article in press: April 23, 2020
Published online: May 26, 2020
Processing time: 92 Days and 4.9 Hours
Abstract
BACKGROUND

Intrauterine adhesion (IUA) can cause serious damage to women's reproductive health, yet current treatment methods are difficult to achieve satisfactory results. In our previous studies, we demonstrated that menstrual-derived stromal stem cells (MenSCs), with high proliferative capacity and self-renewal ability, have a powerful therapeutic effect in patients with severe IUA. However, safety assessment of MenSCs transplantation is essential for its further application.

AIM

To evaluate the short-, medium-, and long-term biosafety of MenSCs via intrauterine transplantation in a rat model of IUA, with a focus on toxicity and tumorigenicity.

METHODS

MenSCs were injected into the sub-serosal layer of the uterus in an IUA rat model, for 3 d, 3 mo, and 6 mo separately, to monitor the corresponding acute, sub-chronic, and chronic effects. Healthy rats of the same age served as negative controls. Toxicity effects were evaluated by body weight, organ weight, histopathology, hematology, and biochemistry tests. Tumorigenicity of MenSCs was investigated in Balb/c-nu mice in vivo and by colony formation assays in vitro.

RESULTS

Compared with the same week-old control group, all of the IUA rats receiving MenSC transplantation demonstrated no obvious changes in body weight, main organ weight, or blood cell composition during the acute, sub-chronic, and chronic observation periods. At the same time, serum biochemical tests showed no adverse effects on metabolism or liver and kidney function. After 4 wk of subcutaneous injection of MenSCs in Balb/c-nu nude mice, no tumor formation or cell metastasis was observed. Moreover, there was no tumor colony formation of MenSCs during soft agar culture in vitro.

CONCLUSION

There is no acute, sub-chronic, or chronic poisoning, infection, tumorigenesis, or endometriosis in rats with IUA after MenSC transplantation. The above results suggest that intrauterine transplantation of MenSCs is safe for endometrial treatment.

Keywords: Menstrual blood-derived stromal cells; Endometrial treatment; Intrauterine adhesion; Stem cell transplantation; Biosafety; Toxicity

Core tip: Menstrual-derived stromal stem cells (MenSCs) with high proliferative capacity and self-renewal ability have a powerful therapeutic effect in patients with severe intrauterine adhesion. However, safety assessment of MenSC transplantation is essential for its further application. Here, we evaluated the short-, medium-, and long-term biosafety of MenSCs via intrauterine transplantation in an intrauterine adhesion rat model, with a special focus on toxicity and tumorigenicity. There was no acute, sub-chronic, or chronic poisoning, infection, tumor, or endometriosis in rats with intrauterine adhesions after MenSC transplantation, highlighting that intrauterine transplantation of MenSCs is safe for endometrial treatment.