Li H, Ji XQ, Zhang SM, Bi RH. Hypoxia and inflammatory factor preconditioning enhances the immunosuppressive properties of human umbilical cord mesenchymal stem cells. World J Stem Cells 2023; 15(11): 999-1016 [PMID: 38058960 DOI: 10.4252/wjsc.v15.i11.999]
Corresponding Author of This Article
Ri-Hui Bi, MD, Surgeon, Department of Hepatobiliary Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Hospital Affiliated to Shanxi Medical University, The Third Hospital of Shanxi Medical University, No. 99 Longcheng, Xiaodian District, Taiyuan 030002, Shanxi Province, China. birihui@sxmu.edu.cn
Research Domain of This Article
Immunology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
World J Stem Cells. Nov 26, 2023; 15(11): 999-1016 Published online Nov 26, 2023. doi: 10.4252/wjsc.v15.i11.999
Hypoxia and inflammatory factor preconditioning enhances the immunosuppressive properties of human umbilical cord mesenchymal stem cells
Hang Li, Xiao-Qing Ji, Shu-Ming Zhang, Ri-Hui Bi
Hang Li, Department of Histology and Embryology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
Xiao-Qing Ji, Shu-Ming Zhang, School of Pharmaceutical Science, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
Ri-Hui Bi, Department of Hepatobiliary Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Hospital Affiliated to Shanxi Medical University, The Third Hospital of Shanxi Medical University, Taiyuan 030002, Shanxi Province, China
Author contributions: Li H, Ji XQ, Zhang SM, and Bi RH designed and coordinated the study; Li H performed experiments and wrote the manuscript; Ji XQ acquired and analyzed the data; Bi RH contributed to ideas, supervision, review and editing; All authors approved the final version of the article.
Supported bythe National Natural Science Foundation of China, No. 31200899.
Institutional review board statement: This study was approved by the Medical Ethics Committee of Shanxi Medical University (Approval No. 2018LL016).
Conflict-of-interest statement: The authors report no relevant conflicts of interest for this article.
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: Ri-Hui Bi, MD, Surgeon, Department of Hepatobiliary Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Hospital Affiliated to Shanxi Medical University, The Third Hospital of Shanxi Medical University, No. 99 Longcheng, Xiaodian District, Taiyuan 030002, Shanxi Province, China. birihui@sxmu.edu.cn
Received: August 15, 2023 Peer-review started: August 15, 2023 First decision: September 5, 2023 Revised: September 28, 2023 Accepted: October 30, 2023 Article in press: October 30, 2023 Published online: November 26, 2023 Processing time: 100 Days and 21.3 Hours
ARTICLE HIGHLIGHTS
Research background
Mesenchymal stem cells (MSCs) have great potential in the treatment of a variety of immune-related diseases due to their unique immunomodulatory and anti-inflammatory abilities. However, after intravenous transplantation, MSCs cannot effectively exert their biological effects when they encounter a harsh environment in vivo, which reduces the efficacy of cell therapy. To increase transplantation efficacy, appropriate pretreatment methods are particularly important.
Research motivation
Although a variety of pretreatment methods are used to increase MSC transplantation efficacy, suitable and effective in vitro pretreatment methods are still worth studying.
Research objectives
To evaluate whether umbilical cord MSCs (UC-MSCs) pretreated with hypoxia exposure and inflammatory factors show enhanced immunosuppressive effects without affecting cell biological characteristics.
Research methods
In this study, we used a combination of hypoxia (2% O2) and inflammatory factors (interleukin-1β, tumor necrosis factor-α, interferon-γ) to pretreat UC-MSCs for 24 h to simulate the in vivo injury environment. We then comprehensively evaluated the biological properties of pretreated UC-MSCs and investigated their immunosuppressive properties.
Research results
Our results showed that compared to UC-MSCs, pretreated UC-MSCs were morphologically elongated, but their viability, proliferation and size were not affected, the expression of coagulation-related tissue factors was significantly reduced, and mitochondria maintained their function and integrity. Although some cells underwent apoptosis or senescence, polymerase chain reactions and enzyme-linked immunosorbent assays revealed a significant increase in the levels of immunomodulation-related factors. Coculture with peripheral blood mononuclear cell and natural killer cells exerted a stronger immunosuppressive effect.
Research conclusions
The combined pretreatment of hypoxia exposure and inflammatory factors enhanced the immunosuppressive ability of MSCs but did not affect the biological characteristics of these cells.
Research perspectives
Our study provides new strategies for the preconditioning of UC-MSCs.
