Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jun 26, 2020; 12(6): 471-480
Published online Jun 26, 2020. doi: 10.4252/wjsc.v12.i6.471
Stem cell therapy for COVID-19 and other respiratory diseases: Global trends of clinical trials
Hong-Long Ji, Cong Liu, Run-Zhen Zhao
Hong-Long Ji, Run-Zhen Zhao, Department of Cellular and Molecular Biology, University of Texas Health Science Centre at Tyler, Tyler, TX 75708, United States
Hong-Long Ji, Texas Lung Injury Institute, University of Texas Health Science Centre at Tyler, Tyler, TX 75708, United States
Cong Liu, School of Medicine, Southern University of Science and Technology, Shenzhen 518000, Guangdong Province, China
Author contributions: Ji HL contributed to the conception and design of the study, preparation of the manuscript, and approval of submission; Liu C searched databases, graphed the results, and drafted the manuscript; Zhao RZ searched databases, drafted and edited the manuscript.
Supported by the NIH grants, No. HL87017.
Conflict-of-interest statement: All authors declare no competing financial interests.
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:
Corresponding author: Hong-Long Ji, MD, PhD, Professor, Department of Cellular and Molecular Biology, Texas Lung Injury Institute, University of Texas Health Science Centre at Tyler, 11937 U.S. Highway 271, Tyler, TX 75708, United States.
Received: May 1, 2020
Peer-review started: May 1, 2020
First decision: May 15, 2020
Revised: May 17, 2020
Accepted: May 21, 2020
Article in press: May 21, 2020
Published online: June 26, 2020

Respiratory diseases, including coronavirus disease 2019 and chronic obstructive pulmonary disease (COPD), are leading causes of global fatality. There are no effective and curative treatments, but supportive care only. Cell therapy is a promising therapeutic strategy for refractory and unmanageable pulmonary illnesses, as proved by accumulating preclinical studies. Stem cells consist of totipotent, pluripotent, multipotent, and unipotent cells with the potential to differentiate into cell types requested for repair. Mesenchymal stromal cells, endothelial progenitor cells, peripheral blood stem cells, and lung progenitor cells have been applied to clinical trials. To date, the safety and feasibility of stem cell and extracellular vesicles administration have been confirmed by numerous phase I/II trials in patients with COPD, acute respiratory distress syndrome, bronchial dysplasia, idiopathic pulmonary fibrosis, pulmonary artery hypertension, and silicosis. Five routes and a series of doses have been tested for tolerance and advantages of different regimes. In this review, we systematically summarize the global trends for the cell therapy of common airway and lung diseases registered for clinical trials. The future directions for both new clinical trials and preclinical studies are discussed.

Keywords: Pulmonary diseases, COVID-19, Cell therapy, Exosomes, Clinical trial

Core tip: Preclinical studies demonstrate significant improvement of lung disorders by stem cells and extracellular vesicles. Completed clinical trials show cell-based therapies are safe and tolerant for acute and chronic respiratory diseases. Current challenges for cell therapy of pulmonary illnesses are long-term safety, efficacy, and personal medicines.