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World J Stem Cells. Aug 26, 2021; 13(8): 1058-1071
Published online Aug 26, 2021. doi: 10.4252/wjsc.v13.i8.1058
Therapeutic prospects of mesenchymal stem/stromal cells in COVID-19 associated pulmonary diseases: From bench to bedside
Lei-Sheng Zhang, Yi Yu, Hao Yu, Zhong-Chao Han
Lei-Sheng Zhang, Qianfoshan Hospital & The First Affiliated Hospital, Shandong First Medical University, Jinan 250014, Shandong Province, China
Lei-Sheng Zhang, Yi Yu, Zhong-Chao Han, State Key Laboratory of Experimental Hematology & National Clinical Research Center for Blood Disease, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
Lei-Sheng Zhang, Hao Yu, School of Medicine, Nankai University, Tianjin 300071, China
Lei-Sheng Zhang, Zhong-Chao Han, Precision Medicine Division, Health-Biotech (Tianjin) Stem Cell Research Institute Co., Ltd., Tianjin 301700, China
Yi Yu, The First Affiliated Hospital, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Hao Yu, Zhong-Chao Han, Cell Products of National Engineering Center & National Stem Cell Engineering Research Center, Tianjin IMCELL Stem Cell and Gene Technology Co., Ltd., Tianjin 300457, China
Author contributions: Zhang LS and Yu Y contributed equally to this work; Zhang LS and Yu Y performed data analysis and interpretation, and manuscript writing and revision; Zhang LS, Yu H, and Han ZC conceptualized and designed the study, and approved the final manuscript; all the coauthors have read and approved the publication of the manuscript.
Supported by Shandong Provincial Natural Science Foundation, No. ZR2020QC097; China Postdoctoral Science Foundation, No. 2019M661033; Jiangxi Key New Product Incubation Program Funded by Technical Innovation Guidance Program of Shangrao city, No. 2020G002; Tianjin Science and Technology Project for Overseas Students, No. JH-20180070802; Natural Science Foundation of Tianjin, No. 19JCQNJC12500; Major Project of Fundamental Research Funds of the Central Public Welfare Scientific Research Institutes of the Chinese Academy of Medical Sciences, No. 2018PT31048; Major Project of Fundamental Research Funds of the Central Public Welfare Scientific Research Institutes of the Chinese Academy of Medical Sciences, No. 2019PT310013; National Science and Technology Major Projects of China for “Major New Drugs Innovation and Development”, No. 2014ZX09508002-003; National Natural Science Foundation of China, No. 81330015; and Science and Technology Project of Tianjin, No. 17ZXSCSY00030.
Conflict-of-interest statement: The authors have no conflicts of interest to disclose.
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: Hao Yu, PhD, Associate Professor, School of Medicine, Nankai University, No. 94 Weijin Road, Nankai District, Tianjin 300071, China. yuhao-wuhan@hotmail.com
Received: February 8, 2021
Peer-review started: February 8, 2021
First decision: March 8, 2021
Revised: March 10, 2021
Accepted: April 20, 2021
Article in press: April 20, 2021
Published online: August 26, 2021
Processing time: 192 Days and 21.6 Hours
Abstract

The ongoing outbreak of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 has become a sudden public emergency of international concern and seriously threatens millions of people’s life health. Two current studies have indicated a favorable role for mesenchymal stem/stromal cells (MSCs) in clinical remission of COVID-19 associated pulmonary diseases, yet the systematical elaboration of the therapeutics and underlying mechanism is far from satisfaction. In the present review, we summarize the therapeutic potential of MSCs in COVID-19 associated pulmonary diseases such as pneumonia induced acute lung injury, acute respiratory distress syndrome, and pulmonary fibrosis. Furthermore, we review the underlying mechanism of MSCs including direct- and trans-differentiation, autocrine and paracrine anti-inflammatory effects, homing, and neovascularization, as well as constitutive microenvironment. Finally, we discuss the prospects and supervision of MSC-based cytotherapy for COVID-19 management before large-scale application in clinical practice. Collectively, this review supplies overwhelming new references for understanding the landscapes of MSCs in the remission of COVID-19 associated pulmonary diseases.

Keywords: Mesenchymal stem/stromal cells; COVID-19; Acute lung injury; Acute respiratory distress syndrome; Pulmonary fibrosis; Molecular mechanism

Core Tip: Coronavirus disease 2019 (COVID-19) is a global pandemic and seriously threatens people’s lives. Due to the limitation of current traditional remedies as well as the rapid disease progression, patients with severe pulmonary manifestations and accompanied comorbidities are inclined to worse outcomes. Herein, we review the latest updates of the mesenchymal stem/stromal cells-based cytotherapy for COVID-19 management, and discuss the principles and underlying molecular mechanisms as well, which will collectively benefit the novel comprehensive treatment for COVID-19 cases.