Current Status of Cell-Based Therapies for COVID-19: Evidence From Mesenchymal Stromal Cells in Sepsis and ARDS

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2021 Oct 18

PMID 34659231

Citations 15

Authors

Zhiheng Xu

Yongbo Huang

Jianmeng Zhou

Xiumei Deng

Weiqun He

Xiaoqing Liu

Yimin Li

Nanshan Zhong

Ling Sang

Affiliations

Soon will be listed here.

Abstract

The severe respiratory consequences of the coronavirus disease 2019 (COVID-19) pandemic have prompted the urgent need for novel therapies. Cell-based therapies, primarily using mesenchymal stromal cells (MSCs), have demonstrated safety and potential efficacy in the treatment of critical illness, particularly sepsis and acute respiratory distress syndrome (ARDS). However, there are limited preclinical data for MSCs in COVID-19. Recent studies have shown that MSCs could decrease inflammation, improve lung permeability, enhance microbe and alveolar fluid clearance, and promote lung epithelial and endothelial repair. In addition, MSC-based therapy has shown promising effects in preclinical studies and phase 1 clinical trials in sepsis and ARDS. Here, we review recent advances related to MSC-based therapy in the context of sepsis and ARDS and evaluate the potential value of MSCs as a therapeutic strategy for COVID-19.

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References

Chen J, Zhang X, Xie J, Xue M, Liu L, Yang Y . Overexpression of TGFβ1 in murine mesenchymal stem cells improves lung inflammation by impacting the Th17/Treg balance in LPS-induced ARDS mice. Stem Cell Res Ther. 2020; 11(1):311. PMC: 7374869. DOI: 10.1186/s13287-020-01826-0. View

Wu Z, McGoogan J . Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020; 323(13):1239-1242. DOI: 10.1001/jama.2020.2648. View

Fang X, Neyrinck A, Matthay M, Lee J . Allogeneic human mesenchymal stem cells restore epithelial protein permeability in cultured human alveolar type II cells by secretion of angiopoietin-1. J Biol Chem. 2010; 285(34):26211-22. PMC: 2924032. DOI: 10.1074/jbc.M110.119917. View

Chen J, Hu C, Chen L, Tang L, Zhu Y, Xu X . Clinical Study of Mesenchymal Stem Cell Treatment for Acute Respiratory Distress Syndrome Induced by Epidemic Influenza A (H7N9) Infection: A Hint for COVID-19 Treatment. Engineering (Beijing). 2020; 6(10):1153-1161. PMC: 7102606. DOI: 10.1016/j.eng.2020.02.006. View

McAuley D, Curley G, Hamid U, Laffey J, Abbott J, McKenna D . Clinical grade allogeneic human mesenchymal stem cells restore alveolar fluid clearance in human lungs rejected for transplantation. Am J Physiol Lung Cell Mol Physiol. 2014; 306(9):L809-15. PMC: 4010648. DOI: 10.1152/ajplung.00358.2013. View

Potter D, Miyazawa B, Gibb S, Deng X, Togaratti P, Croze R . Mesenchymal stem cell-derived extracellular vesicles attenuate pulmonary vascular permeability and lung injury induced by hemorrhagic shock and trauma. J Trauma Acute Care Surg. 2017; 84(2):245-256. PMC: 6378956. DOI: 10.1097/TA.0000000000001744. View

Wang G, Cao K, Liu K, Xue Y, Roberts A, Li F . Kynurenic acid, an IDO metabolite, controls TSG-6-mediated immunosuppression of human mesenchymal stem cells. Cell Death Differ. 2017; 25(7):1209-1223. PMC: 6030103. DOI: 10.1038/s41418-017-0006-2. View

Xu X, Jiang W, Chen L, Xu Z, Zhang Q, Zhu M . Evaluation of the safety and efficacy of using human menstrual blood-derived mesenchymal stromal cells in treating severe and critically ill COVID-19 patients: An exploratory clinical trial. Clin Transl Med. 2021; 11(2):e297. PMC: 7839959. DOI: 10.1002/ctm2.297. View

Gonzalez-Rey E, Anderson P, Gonzalez M, Rico L, Buscher D, Delgado M . Human adult stem cells derived from adipose tissue protect against experimental colitis and sepsis. Gut. 2009; 58(7):929-39. DOI: 10.1136/gut.2008.168534. View

10.

Khatri M, Richardson L, Meulia T . Mesenchymal stem cell-derived extracellular vesicles attenuate influenza virus-induced acute lung injury in a pig model. Stem Cell Res Ther. 2018; 9(1):17. PMC: 5789598. DOI: 10.1186/s13287-018-0774-8. View

11.

Chan M, Kuok D, Leung C, Hui K, Valkenburg S, Lau E . Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo. Proc Natl Acad Sci U S A. 2016; 113(13):3621-6. PMC: 4822574. DOI: 10.1073/pnas.1601911113. View

12.

Sun C, Leu S, Hsu S, Zhen Y, Chang L, Tsai C . Mixed serum-deprived and normal adipose-derived mesenchymal stem cells against acute lung ischemia-reperfusion injury in rats. Am J Transl Res. 2015; 7(2):209-31. PMC: 4399087. View

13.

Hao Q, Zhu Y, Monsel A, Gennai S, Lee T, Xu F . Study of Bone Marrow and Embryonic Stem Cell-Derived Human Mesenchymal Stem Cells for Treatment of Escherichia coli Endotoxin-Induced Acute Lung Injury in Mice. Stem Cells Transl Med. 2015; 4(7):832-40. PMC: 4479628. DOI: 10.5966/sctm.2015-0006. View

14.

Wu K, Wu H, Chao W, Lo W, Tseng P, Lee C . Time-Series Expression of Toll-Like Receptor 4 Signaling in Septic Mice Treated with Mesenchymal Stem Cells. Shock. 2015; 45(6):634-40. DOI: 10.1097/SHK.0000000000000546. View

15.

Li J, Wu X . Mesenchymal stem cells ameliorate LPS-induced acute lung injury through KGF promoting alveolar fluid clearance of alveolar type II cells. Eur Rev Med Pharmacol Sci. 2015; 19(13):2368-78. View

16.

Huleihel L, Sellares J, Cardenes N, Alvarez D, Faner R, Sakamoto K . Modified mesenchymal stem cells using miRNA transduction alter lung injury in a bleomycin model. Am J Physiol Lung Cell Mol Physiol. 2017; 313(1):L92-L103. PMC: 5538868. DOI: 10.1152/ajplung.00323.2016. View

17.

Hall S, Tsoyi K, Ith B, Padera Jr R, Lederer J, Wang Z . Mesenchymal stromal cells improve survival during sepsis in the absence of heme oxygenase-1: the importance of neutrophils. Stem Cells. 2012; 31(2):397-407. PMC: 3572335. DOI: 10.1002/stem.1270. View

18.

Qin H, Zhao A . Mesenchymal stem cell therapy for acute respiratory distress syndrome: from basic to clinics. Protein Cell. 2020; 11(10):707-722. PMC: 7282699. DOI: 10.1007/s13238-020-00738-2. View

19.

Ware L, Matthay M . Alveolar fluid clearance is impaired in the majority of patients with acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med. 2001; 163(6):1376-83. DOI: 10.1164/ajrccm.163.6.2004035. View

20.

Meng F, Xu R, Wang S, Xu Z, Zhang C, Li Y . Human umbilical cord-derived mesenchymal stem cell therapy in patients with COVID-19: a phase 1 clinical trial. Signal Transduct Target Ther. 2020; 5(1):172. PMC: 7450163. DOI: 10.1038/s41392-020-00286-5. View