Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
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 by the 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
Abstract
BACKGROUND

Mesenchymal stem cells (MSCs) have great potential for the treatment of various immune diseases due to their unique immunomodulatory properties. However, MSCs exposed to the harsh inflammatory environment of damaged tissue after intravenous transplantation cannot exert their biological effects, and therefore, their therapeutic efficacy is reduced. In this challenging context, an in vitro preconditioning method is necessary for the development of MSC-based therapies with increased immunomodulatory capacity and transplantation efficacy.

AIM

To determine whether hypoxia and inflammatory factor preconditioning increases the immunosuppressive properties of MSCs without affecting their biological characteristics.

METHODS

Umbilical cord MSCs (UC-MSCs) were pretreated with hypoxia (2% O2) exposure and inflammatory factors (interleukin-1β, tumor necrosis factor-α, interferon-γ) for 24 h. Flow cytometry, polymerase chain reaction, enzyme-linked immunosorbent assay and other experimental methods were used to evaluate the biological characteristics of pretreated UC-MSCs and to determine whether pretreatment affected the immunosuppressive ability of UC-MSCs in coculture with immune cells.

RESULTS

Pretreatment with hypoxia and inflammatory factors caused UC-MSCs to be elongated but did not affect their viability, proliferation or size. In addition, pretreatment significantly decreased the expression of coagulation-related tissue factors but did not affect the expression of other surface markers. Similarly, mitochondrial function and integrity were retained. Although pretreatment promoted UC-MSC apoptosis and senescence, it increased the expression of genes and proteins related to immune regulation. Pretreatment increased peripheral blood mononuclear cell and natural killer (NK) cell proliferation rates and inhibited NK cell-induced toxicity to varying degrees.

CONCLUSION

In summary, hypoxia and inflammatory factor preconditioning led to higher immunosuppressive effects of MSCs without damaging their biological characteristics.

Keywords: Mesenchymal stem cells, Umbilical cord, Preconditioning, Hypoxia, Inflammatory factors, Immune regulation

Core Tip: Mesenchymal stem cells (MSCs) are potential candidates for treating many immune diseases due to their unique immunomodulatory abilities, but low survival rates and weakened function after venous transplantation reduces their treatment potential. Therefore, our study reveals a combination pretreatment method based on in vitro hypoxia exposure and inflammatory factor treatment that simulates the harsh in vivo environment to protect MSCs from injury after intravenous transfusion and promote high immunosuppressive effects of MSCs.