Generic placeholder image

Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Review Article

Mesenchymal Stem Cells Therapy for COVID-19: From Basic Research to Clinical Trial

Author(s): Ya-Chao Tao and En-Qiang Chen*

Volume 19, Issue 1, 2024

Published on: 10 February, 2023

Page: [55 - 62] Pages: 8

DOI: 10.2174/1574888X18666230118122256

Price: $65

conference banner
Abstract

The novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a serious challenge for human health. In severe cases, patients suffer from acute respiratory distress syndrome even organ failure, usually owing to the dysregulated immune response and widespread inflammation. Considering that there is no known cure for COVID-19 despite the increased morbidity and mortality rate of COVID-19, modalities targeting immunity and inflammation may be promising therapeutics against COVID-19. Mesenchymal stem cells (MSCs) possessing immunomodulatory, anti-inflammatory, anti-apoptotic, and antiviral properties, can be of potential benefit to a subset of severe and critically ill patients with COVID-19. In the present study, we described the underlying mechanisms of MSCs therapy and provided a thorough research study on the recent clinical trials of MSCs for SARS-CoV-2 infection.

Graphical Abstract

[1]
Yousefi Dehbidi M, Goodarzi N, Azhdari MH, Doroudian M. Mesenchymal stem cells and their derived exosomes to combat COVID–19. Rev Med Virol 2022; 32(2): e2281.
[http://dx.doi.org/10.1002/rmv.2281] [PMID: 34363275]
[2]
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395(10223): 497-506.
[http://dx.doi.org/10.1016/S0140-6736(20)30183-5] [PMID: 31986264]
[3]
Durand N, Mallea J, Zubair AC. Insights into the use of mesenchymal stem cells in COVID-19 mediated acute respiratory failure. NPJ Regen Med 2020; 5(1): 17.
[http://dx.doi.org/10.1038/s41536-020-00105-z] [PMID: 33580031]
[4]
Boechat JL, Chora I, Morais A, Delgado L. The immune response to SARS-CoV-2 and COVID-19 immunopathology – Current perspectives. Pulmonology 2021; 27(5): 423-37.
[http://dx.doi.org/10.1016/j.pulmoe.2021.03.008] [PMID: 33867315]
[5]
Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP. The trinity of COVID-19: Immunity, inflammation and intervention. Nat Rev Immunol 2020; 20(6): 363-74.
[http://dx.doi.org/10.1038/s41577-020-0311-8] [PMID: 32346093]
[6]
Ellison-Hughes GM, Colley L, O’Brien KA, Roberts KA, Agbaedeng TA, Ross MD. The role of MSC Therapy in attenuating the damaging effects of the cytokine storm induced by COVID-19 on the heart and cardiovascular system. Front Cardiovasc Med 2020; 7: 602183.
[http://dx.doi.org/10.3389/fcvm.2020.602183] [PMID: 33363221]
[7]
Lucas C, Wong P, Klein J, et al. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature 2020; 584(7821): 463-9.
[http://dx.doi.org/10.1038/s41586-020-2588-y] [PMID: 32717743]
[8]
Qin C, Zhou L, Hu Z, et al. Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis 2020; 71(15): 762-8.
[http://dx.doi.org/10.1093/cid/ciaa248] [PMID: 32161940]
[9]
Jamal M, Bangash HI, Habiba M, et al. Immune dysregulation and system pathology in COVID-19. Virulence 2021; 12(1): 918-36.
[http://dx.doi.org/10.1080/21505594.2021.1898790] [PMID: 33757410]
[10]
Patterson BK, Guevara-Coto J, Yogendra R, et al. Immune-based prediction of COVID-19 severity and chronicity decoded using machine learning. Front Immunol 2021; 12: 700782.
[http://dx.doi.org/10.3389/fimmu.2021.700782] [PMID: 34262570]
[11]
Liu J, Li S, Liu J, et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine 2020; 55: 102763.
[http://dx.doi.org/10.1016/j.ebiom.2020.102763] [PMID: 32361250]
[12]
Yang Y, Shen C, Li J, et al. Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19. J Allergy Clin Immunol 2020; 146(1): 119-127.e4.
[http://dx.doi.org/10.1016/j.jaci.2020.04.027] [PMID: 32360286]
[13]
Chen G, Wu D, Guo W, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest 2020; 130(5): 2620-9.
[http://dx.doi.org/10.1172/JCI137244] [PMID: 32217835]
[14]
Monguió-Tortajada M, Bayes-Genis A, Rosell A, Roura S. Are mesenchymal stem cells and derived extracellular vesicles valuable to halt the COVID-19 inflammatory cascade? Current evidence and future perspectives. Thorax 2021; 76(2): 196-200.
[http://dx.doi.org/10.1136/thoraxjnl-2020-215717] [PMID: 33323479]
[15]
Jamaati H, Hashemian SM, Farzanegan B, et al. No clinical benefit of high dose corticosteroid administration in patients with COVID-19: A preliminary report of a randomized clinical trial. Eur J Pharmacol 2021; 897: 173947.
[http://dx.doi.org/10.1016/j.ejphar.2021.173947] [PMID: 33607104]
[16]
Najar M, Melki R, Khalife F, et al. Therapeutic mesenchymal stem/stromal cells: Value, challenges and optimization. Front Cell Dev Biol 2022; 9: 716853.
[http://dx.doi.org/10.3389/fcell.2021.716853] [PMID: 35096805]
[17]
Chen L, Qu J, Kalyani FS, et al. Mesenchymal stem cell-based treatments for COVID-19: Status and future perspectives for clinical applications. Cell Mol Life Sci 2022; 79(3): 142.
[http://dx.doi.org/10.1007/s00018-021-04096-y] [PMID: 35187617]
[18]
Li Z, Niu S, Guo B, et al. Stem cell therapy for COVID‐19, ARDS and pulmonary fibrosis. Cell Prolif 2020; 53(12): e12939.
[http://dx.doi.org/10.1111/cpr.12939] [PMID: 33098357]
[19]
Wu X, Dao Thi VL, Huang Y, et al. Intrinsic immunity shapes viral resistance of stem cells. Cell 2018; 172(3): 423-438.e25.
[http://dx.doi.org/10.1016/j.cell.2017.11.018] [PMID: 29249360]
[20]
Li N, Hua J. Interactions between mesenchymal stem cells and the immune system. Cell Mol Life Sci 2017; 74(13): 2345-60.
[http://dx.doi.org/10.1007/s00018-017-2473-5] [PMID: 28214990]
[21]
Jung YJ, Park YY, Huh JW, Hong SB. The effect of human adipose-derived stem cells on lipopolysaccharide-induced acute respiratory distress syndrome in mice. Ann Transl Med 2019; 7(22): 674.
[http://dx.doi.org/10.21037/atm.2019.10.48] [PMID: 31930075]
[22]
Xu H, Nie G, Yin T, Shao C, Ding D, Zou M. Umbilical cord-derived mesenchymal stem cells with surfactant protein B alleviates inflammatory response in acute respiratory distress syndrome by regulating macrophage polarization. Balkan Med J 2022; 39(1): 130-9.
[PMID: 35330560]
[23]
Lu Z, Chang W, Meng S, et al. Mesenchymal stem cells induce dendritic cell immune tolerance via paracrine hepatocyte growth factor to alleviate acute lung injury. Stem Cell Res Ther 2019; 10(1): 372.
[http://dx.doi.org/10.1186/s13287-019-1488-2] [PMID: 31801626]
[24]
Leng Z, Zhu R, Hou W, et al. Transplantation of ACE2- mesenchymal stem cells improves the outcome of patients with COVID-19 pneumonia. Aging Dis 2020; 11(2): 216-28.
[http://dx.doi.org/10.14336/AD.2020.0228] [PMID: 32257537]
[25]
Zhu R, Yan T, Feng Y, et al. Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms. Cell Res 2021; 31(12): 1244-62.
[http://dx.doi.org/10.1038/s41422-021-00573-y] [PMID: 34702946]
[26]
Sánchez-Guijo F, García-Arranz M, López-Parra M, et al. Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study. EClinicalMedicine 2020; 25: 100454.
[http://dx.doi.org/10.1016/j.eclinm.2020.100454] [PMID: 32838232]
[27]
Shu L, Niu C, Li R, et al. Treatment of severe COVID-19 with human umbilical cord mesenchymal stem cells. Stem Cell Res Ther 2020; 11(1): 361.
[http://dx.doi.org/10.1186/s13287-020-01875-5] [PMID: 32811531]
[28]
Dilogo IH, Aditianingsih D, Sugiarto A, et al. Umbilical cord mesenchymal stromal cells as critical COVID-19 adjuvant therapy: A randomized controlled trial. Stem Cells Transl Med 2021; 10(9): 1279-87.
[http://dx.doi.org/10.1002/sctm.21-0046] [PMID: 34102020]
[29]
Lanzoni G, Linetsky E, Correa D, et al. Umbilical cord mesenchymal stem cells for COVID-19 acute respiratory distress syndrome: A double-blind, phase 1/2a, randomized controlled trial. Stem Cells Transl Med 2021; 10(5): 660-73.
[http://dx.doi.org/10.1002/sctm.20-0472] [PMID: 33400390]
[30]
Hao D, He C, Ma B, et al. Hypoxic preconditioning enhances survival and proangiogenic capacity of human first trimester chorionic villus-derived mesenchymal stem cells for fetal tissue engineering. Stem Cells Int 2019; 2019: 9695239.
[http://dx.doi.org/10.1155/2019/9695239] [PMID: 31781252]
[31]
Cañas-Arboleda M, Beltrán K, Medina C, Camacho B, Salguero G. Human platelet lysate supports efficient expansion and stability of Wharton’s jelly mesenchymal stromal cells via active uptake and release of soluble regenerative factors. Int J Mol Sci 2020; 21(17): 6284.
[http://dx.doi.org/10.3390/ijms21176284] [PMID: 32877987]
[32]
Sahan OB, Gunel-Ozcan A. Hepatocyte growth factor and insulin-like growth factor-1 based cellular therapies for oxidative stress injury. Curr Stem Cell Res Ther 2021; 16(7): 771-91.
[http://dx.doi.org/10.2174/1574888X16999201124153753] [PMID: 33238860]
[33]
Yang Y, Hu S, Xu X, et al. The vascular endothelial growth factors-expressing character of mesenchymal stem cells plays a positive role in treatment of acute lung injury in vivo. Mediators Inflamm 2016; 2016: 2347938.
[http://dx.doi.org/10.1155/2016/2347938] [PMID: 27313398]
[34]
Bernard O, Jeny F, Uzunhan Y, et al. Mesenchymal stem cells reduce hypoxia-induced apoptosis in alveolar epithelial cells by modulating HIF and ROS hypoxic signaling. Am J Physiol Lung Cell Mol Physiol 2018; 314(3): L360-71.
[http://dx.doi.org/10.1152/ajplung.00153.2017] [PMID: 29167125]
[35]
Klimczak A. Perspectives on mesenchymal stem/progenitor cells and their derivates as potential therapies for lung damage caused by COVID-19. World J Stem Cells 2020; 12(9): 1013-22.
[http://dx.doi.org/10.4252/wjsc.v12.i9.1013] [PMID: 33033561]
[36]
Liu J, Peng D, You J, et al. Type 2 alveolar epithelial cells differentiated from human umbilical cord mesenchymal stem cells alleviate mouse pulmonary fibrosis through β-catenin-regulated cell apoptosis. Stem Cells Dev 2021; 30(13): 660-70.
[http://dx.doi.org/10.1089/scd.2020.0208] [PMID: 33899513]
[37]
Fujioka N, Kitabatake M, Ouji-Sageshima N, et al. Human adipose-derived mesenchymal stem cells ameliorate elastase-induced emphysema in mice by mesenchymal–epithelial transition. Int J Chron Obstruct Pulmon Dis 2021; 16: 2783-93.
[http://dx.doi.org/10.2147/COPD.S324952] [PMID: 34675503]
[38]
Bailey CC, Zhong G, Huang IC, Farzan M. IFITM-family proteins: The cell’s first line of antiviral defense. Annu Rev Virol 2014; 1(1): 261-83.
[http://dx.doi.org/10.1146/annurev-virology-031413-085537] [PMID: 25599080]
[39]
Richardson RB, Ohlson MB, Eitson JL, et al. A CRISPR screen identifies IFI6 as an ER-resident interferon effector that blocks flavivirus replication. Nat Microbiol 2018; 3(11): 1214-23.
[http://dx.doi.org/10.1038/s41564-018-0244-1] [PMID: 30224801]
[40]
Singh PK, Singh S, Farr D, Kumar A. Interferon-stimulated gene 15 (ISG15) restricts Zika virus replication in primary human corneal epithelial cells. Ocul Surf 2019; 17(3): 551-9.
[http://dx.doi.org/10.1016/j.jtos.2019.03.006] [PMID: 30905842]
[41]
Khatri M, Richardson LA, 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.
[http://dx.doi.org/10.1186/s13287-018-0774-8] [PMID: 29378639]
[42]
Oh SJ, Lee EN, Park JH, et al. Anti-viral activities of umbilical cord mesenchymal stem cell-derived small extracellular vesicles against human respiratory viruses. Front Cell Infect Microbiol 2022; 12: 850744.
[http://dx.doi.org/10.3389/fcimb.2022.850744] [PMID: 35558099]
[43]
Meng F, Xu R, Wang S, et al. 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.
[http://dx.doi.org/10.1038/s41392-020-00286-5] [PMID: 32855385]
[44]
Häberle H, Magunia H, Lang P, et al. Mesenchymal stem cell therapy for severe COVID-19 ARDS. J Intensive Care Med 2021; 36(6): 681-8.
[http://dx.doi.org/10.1177/0885066621997365] [PMID: 33663244]
[45]
Monsel A, Hauw-Berlemont C, Mebarki M, et al. Treatment of COVID-19-associated ARDS with mesenchymal stromal cells: A multicenter randomized double-blind trial. Crit Care 2022; 26(1): 48.
[http://dx.doi.org/10.1186/s13054-022-03930-4] [PMID: 35189925]
[46]
Xu X, Jiang W, Chen L, et al. 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.
[http://dx.doi.org/10.1002/ctm2.297] [PMID: 33634996]
[47]
Hashemian SMR, Aliannejad R, Zarrabi M, et al. Mesenchymal stem cells derived from perinatal tissues for treatment of critically ill COVID-19-induced ARDS patients: A case series. Stem Cell Res Ther 2021; 12(1): 91.
[http://dx.doi.org/10.1186/s13287-021-02165-4] [PMID: 33514427]
[48]
Saleh M, Vaezi AA, Aliannejad R, et al. Cell therapy in patients with COVID-19 using Wharton’s jelly mesenchymal stem cells: A phase 1 clinical trial. Stem Cell Res Ther 2021; 12(1): 410.
[http://dx.doi.org/10.1186/s13287-021-02483-7] [PMID: 34271988]
[49]
Shi L, Huang H, Lu X, et al. Effect of human umbilical cord-derived mesenchymal stem cells on lung damage in severe COVID-19 patients: A randomized, double-blind, placebo-controlled phase 2 trial. Signal Transduct Target Ther 2021; 6(1): 58.
[http://dx.doi.org/10.1038/s41392-021-00488-5] [PMID: 33568628]
[50]
Feng Y, Huang J, Wu J, et al. Safety and feasibility of umbilical cord mesenchymal stem cells in patients with COVID‐19 pneumonia: A pilot study. Cell Prolif 2020; 53(12): e12947.
[http://dx.doi.org/10.1111/cpr.12947] [PMID: 33205469]
[51]
Kaffash Farkhad N, Sedaghat A, Reihani H, et al. Mesenchymal stromal cell therapy for COVID-19-induced ARDS patients: A successful phase 1, control-placebo group, clinical trial. Stem Cell Res Ther 2022; 13(1): 283.
[http://dx.doi.org/10.1186/s13287-022-02920-1] [PMID: 35765103]
[52]
Rebelatto CLK, Senegaglia AC, Franck CL, et al. Safety and long-term improvement of mesenchymal stromal cell infusion in critically COVID-19 patients: A randomized clinical trial. Stem Cell Res Ther 2022; 13(1): 122.
[http://dx.doi.org/10.1186/s13287-022-02796-1] [PMID: 35313959]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy