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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Review Article

Clinical Consideration for Mesenchymal Stem Cells in Treatment of COVID-19

Author(s): Kang-Hsi Wu*, Yu-Hua Chao, Te-Fu Weng and Ju-Pi Li

Volume 28, Issue 36, 2022

Published on: 04 October, 2022

Page: [2991 - 2994] Pages: 4

DOI: 10.2174/1381612828666220926094730

Price: $65

Abstract

COVID-19, which has strongly affected the 21st century, is caused by severe acute respiratory syndrome (SARS)-CoV-2. The emergence of viral variants has rendered even vaccinated people prone to infection; thus, completely eradicating COVID-19 may be impossible. COVID-19 causes hyperinflammation, leading to organ damage and even death. SARS-CoV-2 infects not only the lungs, causing acute respiratory distress syndrome, but also the extrapulmonary organs. Not all patients with COVID-19 respond adequately to treatments with antiviral and anti-inflammatory drugs. Therefore, new treatments are urgently needed. Mesenchymal stem cells (MSCs) exhibit immunomodulatory activity and are used to safely and effectively treat various immune disorders. Evidence has indicated the efficacy of MSCs against COVID-19. However, the safety and efficacy of MSCs must be probed further. For this reason, we explored key clinical challenges associated with MSC therapy for COVID-19, such as sources, administration routes, cell dosage, treatment timepoint, and virus reactivation. We identified several challenges that must be addressed before MSCs can be clinically applied.

Keywords: Mesenchymal stem cells, COVID-19, hyperinflammation, immunomodulation, clinical consideration, treatment.

« Previous Next »
[1]
Singh S, McNab C, Olson RM, et al. How an outbreak became a pandemic: A chronological analysis of crucial junctures and international obligations in the early months of the COVID-19 pandemic. Lancet 2021; 398(10316): 2109-24.
[http://dx.doi.org/10.1016/S0140-6736(21)01897-3] [PMID: 34762857]
[2]
Berlin DA, Gulick RM, Martinez FJ. Severe COVID-19. N Engl J Med 2020; 383(25): 2451-60.
[http://dx.doi.org/10.1056/NEJMcp2009575] [PMID: 32412710]
[3]
Burki TK. The race between vaccination and evolution of COVID-19 variants. Lancet Respir Med 2021; 9(11): e109.
[http://dx.doi.org/10.1016/S2213-2600(21)00443-4] [PMID: 34597533]
[4]
Kuri-Cervantes L, Pampena MB, Meng W, et al. Comprehensive mapping of immune perturbations associated with severe COVID-19. Sci Immunol 2020; 5(49): eabd7114.
[http://dx.doi.org/10.1126/sciimmunol.abd7114] [PMID: 32669287]
[5]
Mathew D, Giles JR, Baxter AE, et al. Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science 2020; 369(6508): eabc8511.
[http://dx.doi.org/10.1126/science.abc8511] [PMID: 32669297]
[6]
Moore JB, June CH. Cytokine release syndrome in severe COVID-19. Science 2020; 368(6490): 473-4.
[http://dx.doi.org/10.1126/science.abb8925] [PMID: 32303591]
[7]
Song JW, Zhang C, Fan X, et al. Immunological and inflammatory profiles in mild and severe cases of COVID-19. Nat Commun 2020; 11(1): 3410.
[http://dx.doi.org/10.1038/s41467-020-17240-2] [PMID: 32641700]
[8]
Vabret N, Britton GJ, Gruber C, et al. Immunology of COVID-19: Current state of the science. Immunity 2020; 52(6): 910-41.
[http://dx.doi.org/10.1016/j.immuni.2020.05.002] [PMID: 32505227]
[9]
Horby P, Lim WS, Emberson JR, et al. Dexamethasone in hospitalized patients with COVID-19. N Engl J Med 2021; 384(8): 693-704.
[http://dx.doi.org/10.1056/NEJMoa2021436] [PMID: 32678530]
[10]
Salama C, Han J, Yau L, et al. Tocilizumab in patients hospitalized with COVID-19 Pneumonia. N Engl J Med 2021; 384(1): 20-30.
[http://dx.doi.org/10.1056/NEJMoa2030340] [PMID: 33332779]
[11]
Krampera M, Le Blanc K. Mesenchymal stromal cells: Putative microenvironmental modulators become cell therapy. Cell Stem Cell 2021; 28(10): 1708-25.
[http://dx.doi.org/10.1016/j.stem.2021.09.006] [PMID: 34624232]
[12]
Nauta AJ, Fibbe WE. Immunomodulatory properties of mesenchymal stromal cells. Blood 2007; 110(10): 3499-506.
[http://dx.doi.org/10.1182/blood-2007-02-069716] [PMID: 17664353]
[13]
Bernardo ME, Fibbe WE. Mesenchymal stromal cells: Sensors and switchers of inflammation. Cell Stem Cell 2013; 13(4): 392-402.
[http://dx.doi.org/10.1016/j.stem.2013.09.006] [PMID: 24094322]
[14]
Le Blanc K, Frassoni F, Ball L, et al. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: A phase II study. Lancet 2008; 371(9624): 1579-86.
[http://dx.doi.org/10.1016/S0140-6736(08)60690-X] [PMID: 18468541]
[15]
Hashmi S, Ahmed M, Murad MH, et al. Survival after mesenchymal stromal cell therapy in steroid-refractory acute graft-versus-host disease: Systematic review and meta-analysis. Lancet Haematol 2016; 3(1): e45-52.
[http://dx.doi.org/10.1016/S2352-3026(15)00224-0] [PMID: 26765648]
[16]
Trounson A, McDonald C. Stem cell therapies in clinical trials: Progress and challenges. Cell Stem Cell 2015; 17(1): 11-22.
[http://dx.doi.org/10.1016/j.stem.2015.06.007] [PMID: 26140604]
[17]
Galipeau J, Sensébé L. Mesenchymal stromal cells: Clinical challenges and therapeutic opportunities. Cell Stem Cell 2018; 22(6): 824-33.
[http://dx.doi.org/10.1016/j.stem.2018.05.004] [PMID: 29859173]
[18]
Liang J, Zhang H, Hua B, et al. Allogenic mesenchymal stem cells transplantation in refractory systemic lupus erythematosus: A pilot clinical study. Ann Rheum Dis 2010; 69(8): 1423-9.
[http://dx.doi.org/10.1136/ard.2009.123463] [PMID: 20650877]
[19]
Sun L, Wang D, Liang J, et al. Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus. Arthritis Rheum 2010; 62(8): 2467-75.
[http://dx.doi.org/10.1002/art.27548] [PMID: 20506343]
[20]
Zhou T, Li HY, Liao C, Lin W, Lin S. Clinical efficacy and safety of mesenchymal stem cells for systemic lupus erythematosus. Stem Cells Int 2020; 2020: 1-11.
[http://dx.doi.org/10.1155/2020/6518508] [PMID: 32322279]
[21]
Chan CK, Wu KH, Lee YS, et al. The comparison of interleukin 6-associated immunosuppressive effects of human ESCs, fetal-type MSCs, and adult-type MSCs. Transplantation 2012; 94(2): 132-8.
[http://dx.doi.org/10.1097/TP.0b013e31825940a4] [PMID: 22766769]
[22]
Chen X, Shan Y, Wen Y, Sun J, Du H. Mesenchymal stem cell therapy in severe COVID-19: A retrospective study of short-term treatment efficacy and side effects. J Infect 2020; 81(4): 647-79.
[http://dx.doi.org/10.1016/j.jinf.2020.05.020] [PMID: 32422152]
[23]
Guo Z, Chen Y, Luo X, He X, Zhang Y, Wang J. Administration of umbilical cord mesenchymal stem cells in patients with severe COVID-19 pneumonia. Crit Care 2020; 24(1): 420.
[http://dx.doi.org/10.1186/s13054-020-03142-8] [PMID: 32653043]
[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]
Meng F, Xu R, Wang S, et al. Human umbilical cord-derived mesenchymal stem cell therapy in patients with COVID-19: A phase 1 clini-cal trial. Signal Transduct Target Ther 2020; 5(1): 172.
[http://dx.doi.org/10.1038/s41392-020-00286-5] [PMID: 32855385]
[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]
Tang L, Jiang Y, Zhu M, et al. Clinical study using mesenchymal stem cells for the treatment of patients with severe COVID-19. Front Med 2020; 14(5): 664-73.
[http://dx.doi.org/10.1007/s11684-020-0810-9] [PMID: 32761491]
[29]
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]
[30]
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]
[31]
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]
[32]
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]
[33]
Thompson M, Mei SHJ, Wolfe D, et al. Cell therapy with intravascular administration of mesenchymal stromal cells continues to appear safe: An updated systematic review and meta-analysis. eClinicalMedicine 2020; 19: 100249.
[http://dx.doi.org/10.1016/j.eclinm.2019.100249] [PMID: 31989101]
[34]
Powell SB, Silvestri JM. Safety of intratracheal administration of human umbilical cord blood derived mesenchymal stromal cells in extremely low birth weight preterm infants. J Pediatr 2019; 210: 209-213.e2.
[http://dx.doi.org/10.1016/j.jpeds.2019.02.029] [PMID: 30992220]
[35]
Schrepfer S, Deuse T, Reichenspurner H, Fischbein MP, Robbins RC, Pelletier MP. Stem cell transplantation: The lung barrier. Transplant Proc 2007; 39(2): 573-6.
[http://dx.doi.org/10.1016/j.transproceed.2006.12.019] [PMID: 17362785]
[36]
Gupta A, Madhavan MV, Sehgal K, et al. Extrapulmonary manifestations of COVID-19. Nat Med 2020; 26(7): 1017-32.
[http://dx.doi.org/10.1038/s41591-020-0968-3] [PMID: 32651579]
[37]
Puelles VG, Lütgehetmann M, Lindenmeyer MT, et al. Multiorgan and renal tropism of SARS-CoV-2. N Engl J Med 2020; 383(6): 590-2.
[http://dx.doi.org/10.1056/NEJMc2011400] [PMID: 32402155]
[38]
Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020; 395(10234): 1417-8.
[http://dx.doi.org/10.1016/S0140-6736(20)30937-5] [PMID: 32325026]
[39]
Gandhi RT, Lynch JB, del Rio C. Mild or Moderate Covid-19. N Engl J Med 2020; 383(18): 1757-66.
[http://dx.doi.org/10.1056/NEJMcp2009249] [PMID: 32329974]
[40]
Lucchini G, Dander E, Pavan F, et al. Mesenchymal stromal cells do not increase the risk of viral reactivation nor the severity of viral events in recipients of allogeneic stem cell transplantation. Stem Cells Int 2012; 2012: 1-6.
[http://dx.doi.org/10.1155/2012/690236] [PMID: 22701127]

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