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Current Stem Cell Research & Therapy

Editor-in-Chief

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

Mini-Review Article

Positive Aspects, Negative Aspects and Challenges Associated with Stem Cell Therapy for COVID - 19: A Mini-review

Author(s): Basavraj Nagoba*, Ajay Gavkare, Abhijit Rayate and Sachin Mumbre

Volume 17, Issue 8, 2022

Published on: 07 December, 2021

Page: [720 - 726] Pages: 7

DOI: 10.2174/1574888X16666211102092039

Price: $65

Abstract

Like any other pandemic, Covid-19 scenario has also demanded effective treatment options. The circumstances demand to utilize all the possible weapons in the armamentarium. There have been many issues regarding the short-term and long-term safety and efficacy of these options. Some options are like uncharted seas and these need a detailed and critical review with respect to safety, efficacy, feasibility and financial constraints. Mesenchymal stem cells (MSCs) therapy has been studied for many years for its potential role in diseases with complex pathogenesis. Its efficacy in controlling cytokine imbalance and immuno-modulatory properties is well proven. These effects are being extensively studied for potential extension of the benefits for an effective option for management of COVID-19 patients with severe respiratory involvement. In this mini-review, an attempt has been made to review positive aspects, negative aspects, and challenges influencing MSCs therapy in the management of COVID-19 disease. The results of various studies and literature reviews show that MSCs therapy can be considered as one of the potential options.

This article reviews the role of Mesenchymal Stem Cell (MSC) transplantation in critically ill SARS-COV-19 patients with lung involvement. The MSCs counteract the cytokine storm, regulate the immune responses, facilitate the expression of essential growth factors, and eventually improve the local milieu and promote the restoration of pulmonary vascular and alveolar linings for early healing. As with all new therapeutic options, MSC therapy will also have to stand the test of time with respect to safety, specificity, and constraints like mass production and “available for all” at “affordable cost.”

Keywords: COVID-19, mesenchymal stem cell therapy, positive aspects, negative aspects, challenges, SARS-CoV-2.

[1]
WHO. WHO coronavirus disease (COVID-19) dashboard. Geneva World Heal Organ 2021. Available from: https://covid19.who.int/
[2]
Nagoba B, Gavkare A, Jamadar N, Mumbre S, Selkar S. Positive aspects, negative aspects and limitations of plasma therapy with special reference to COVID-19. J Infect Public Health 2020; 13(12): 1818-22.
[http://dx.doi.org/10.1016/j.jiph.2020.08.011] [PMID: 32900666]
[3]
Shen C, Wang Z, Zhao F, et al. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA 2020; 323(16): 1582-9.
[http://dx.doi.org/10.1001/jama.2020.4783] [PMID: 32219428]
[4]
Duan K, Liu B, Li C, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci USA 2020; 117(17): 9490-6.
[http://dx.doi.org/10.1073/pnas.2004168117] [PMID: 32253318]
[5]
Zhang B, Liu S, Tan T, et al. Treatment with convalescent plasma for critically Ill patients with severe acute respiratory syndrome Coronavirus 2 infection. Chest 2020; 158(1): e9-e13.
[http://dx.doi.org/10.1016/j.chest.2020.03.039] [PMID: 32243945]
[6]
Ahn JY, Sohn Y, Lee SH, et al. Use of convalescent plasma therapy in two COVID-19 patients with acute respiratory distress syndrome in Korea. J Korean Med Sci 2020; 35(14): e149.
[http://dx.doi.org/10.3346/jkms.2020.35.e149] [PMID: 32281317]
[7]
Ye M, Fu D, Ren Y, et al. Treatment with convalescent plasma for COVID-19 patients in Wuhan, China. J Med Virol 2020; 92(10): 1890-901.
[http://dx.doi.org/10.1002/jmv.25882] [PMID: 32293713]
[8]
Cohen J, Kupferschmidt K. ‘A very, very bad look’ for remdesivir. Science 2020; 370(6517): 642-3.
[http://dx.doi.org/10.1126/science.370.6517.642] [PMID: 33154114]
[9]
Chrzanowski W, Kim SY, McClements L. Can stem cells beat COVID-19: Advancing stem cells and extracellular vesicles toward mainstream medicine for lung injuries associated with SARS-CoV-2 infections. Front Bioeng Biotechnol 2020; 8: 554.
[http://dx.doi.org/10.3389/fbioe.2020.00554] [PMID: 32574317]
[10]
Golchin A, Seyedjafari E, Ardeshirylajimi A. Mesenchymal stem cell therapy for COVID-19: Present or future. Stem Cell Rev Rep 2020; 16(3): 427-33.
[http://dx.doi.org/10.1007/s12015-020-09973-w] [PMID: 32281052]
[11]
Metcalfe SM. Mesenchymal stem cells and management of COVID-19 pneumonia. Med drug Discov 2020; 5: 100019.
[http://dx.doi.org/10.1016/j.medidd.2020.100019]
[12]
Li H, Liu L, Zhang D, et al. SARS-CoV-2 and viral sepsis: Observations and hypotheses. Lancet 2020; 395(10235): 1517-20.
[http://dx.doi.org/10.1016/S0140-6736(20)30920-X] [PMID: 32311318]
[13]
Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost 2020; 18(4): 844-7.
[http://dx.doi.org/10.1111/jth.14768] [PMID: 32073213]
[14]
Bian X-W, Yao X-H, Ping Y-F. Autopsy of COVID-19 patients in China. Natl Sci Rev 2020; 7(9): 1414-8.
[http://dx.doi.org/10.1093/nsr/nwaa123] [PMID: 34192086]
[15]
Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020; 8(4): 420-2.
[http://dx.doi.org/10.1016/S2213-2600(20)30076-X] [PMID: 32085846]
[16]
Li C, Zhao H, Wang B. Challenges for mesenchymal stem cell-based therapy for COVID-19. Drug Des Devel Ther 2020; 14: 3995-4001.
[http://dx.doi.org/10.2147/DDDT.S269407] [PMID: 33061304]
[17]
Chuang H-M, Shih TE, Lu K-Y, Tsai S-F, Harn H-J, Ho L-I. Mesenchymal stem cell therapy of pulmonary fibrosis: Improvement with target combination. Cell Transplant 2018; 27(11): 1581-7.
[http://dx.doi.org/10.1177/0963689718787501] [PMID: 29991279]
[18]
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020; 395(10229): 1033-4.
[http://dx.doi.org/10.1016/S0140-6736(20)30628-0] [PMID: 32192578]
[19]
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]
[20]
Ye Q, Wang B, Mao J. The pathogenesis and treatment of the ‘Cytokine Storm’ in COVID-19. J Infect 2020; 80(6): 607-13.
[http://dx.doi.org/10.1016/j.jinf.2020.03.037] [PMID: 32283152]
[21]
Klok FA, Kruip MJHA, van der Meer NJM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res 2020; 191: 145-7.
[http://dx.doi.org/10.1016/j.thromres.2020.04.013] [PMID: 32291094]
[22]
Klok FA, Kruip MJHA, van der Meer NJM, et al. Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: An updated analysis. Thromb Res 2020; 191: 148-50.
[http://dx.doi.org/10.1016/j.thromres.2020.04.041] [PMID: 32381264]
[23]
Beyrouti R, Adams ME, Benjamin L, et al. Characteristics of ischaemic stroke associated with COVID-19. J Neurol Neurosurg Psychiatry 2020; 91(8): 889-91.
[http://dx.doi.org/10.1136/jnnp-2020-323586] [PMID: 32354768]
[24]
Choudhery MS, Harris DT. Stem cell therapy for COVID-19: Possibilities and challenges. Cell Biol Int 2020; 44(11): 2182-91.
[http://dx.doi.org/10.1002/cbin.11440] [PMID: 32767687]
[25]
Moore JB, June CH. Cytokine release syndrome in severe COVID-19. Science (80- ) 2020; 368: 473-4.
[http://dx.doi.org/10.1126/science.abb8925]
[26]
Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA 2020; 323(11): 1061-9.
[http://dx.doi.org/10.1001/jama.2020.1585] [PMID: 32031570]
[27]
Sun X, Wang T, Cai D, et al. Cytokine storm intervention in the early stages of COVID-19 pneumonia. Cytokine Growth Factor Rev 2020; 53: 38-42.
[http://dx.doi.org/10.1016/j.cytogfr.2020.04.002] [PMID: 32360420]
[28]
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]
[29]
Liang B, Chen J, Li T, et al. Clinical remission of a critically ill COVID-19 patient treated by human umbilical cord mesenchymal stem cells: A case report. Medicine (Baltimore) 2020; 99(31): e21429.
[http://dx.doi.org/10.1097/MD.0000000000021429] [PMID: 32756149]
[30]
Shetty AK. Mesenchymal stem cell infusion shows promise for combating Coronavirus (COVID-19)-induced pneumonia. Aging Dis 2020; 11(2): 462-4.
[http://dx.doi.org/10.14336/AD.2020.0301] [PMID: 32257554]
[31]
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]
[32]
Khoury M, Cuenca J, Cruz FF, Figueroa FE, Rocco PRM, Weiss DJ. Current status of cell-based therapies for respiratory virus infections: Applicability to COVID-19. Eur Respir J 2020; 55(6): 2000858.
[http://dx.doi.org/10.1183/13993003.00858-2020] [PMID: 32265310]
[33]
Fan BE, Chong VCL, Chan SSW, et al. Hematologic parameters in patients with COVID-19 infection. Am J Hematol 2020; 95(6): E131-4.
[http://dx.doi.org/10.1002/ajh.25774] [PMID: 32129508]
[34]
Zhai P, Ding Y, Wu X, Long J, Zhong Y, Li Y. The epidemiology, diagnosis and treatment of COVID-19. Int J Antimicrob Agents 2020; 55(5): 105955.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105955] [PMID: 32234468]
[35]
Rajarshi K, Chatterjee A, Ray S. Combating COVID-19 with mesenchymal stem cell therapy. Biotechnol Rep (Amst) 2020; 26: e00467.
[http://dx.doi.org/10.1016/j.btre.2020.e00467] [PMID: 32420049]
[36]
Abraham A, Krasnodembskaya A. Mesenchymal stem cell-derived extracellular vesicles for the treatment of acute respiratory distress syndrome. Stem Cells Transl Med 2020; 9(1): 28-38.
[http://dx.doi.org/10.1002/sctm.19-0205] [PMID: 31647191]
[37]
Esquivel D, Mishra R, Srivastava A. Stem cell therapy offers a possible safe and promising alternative approach for treating Vitiligo: A review. Curr Pharm Des 2020; 26(37): 4815-21.
[http://dx.doi.org/10.2174/1381612826666200730221446] [PMID: 32744962]
[38]
Fayyad-Kazan H, Faour WH, Badran B, Lagneaux L, Najar M. The immunomodulatory properties of human bone marrow-derived mesenchymal stromal cells are defined according to multiple immunobiological criteria. Inflamm Res 2016; 65(6): 501-10.
[http://dx.doi.org/10.1007/s00011-016-0933-2] [PMID: 26956767]
[39]
Uccelli A, de Rosbo NK. The immunomodulatory function of mesenchymal stem cells: mode of action and pathways. Ann N Y Acad Sci 2015; 1351: 114-26.
[http://dx.doi.org/10.1111/nyas.12815] [PMID: 26152292]
[40]
Khare D, Or R, Resnick I, Barkatz C, Almogi-Hazan O, Avni B. Mesenchymal stromal cell-derived exosomes affect mRNA expression and function of B-lymphocytes. Front Immunol 2018; 9: 3053.
[http://dx.doi.org/10.3389/fimmu.2018.03053] [PMID: 30622539]
[41]
Li J, Wang X, Li N, et al. Feasibility of mesenchymal stem cell therapy for COVID-19: A mini review. Curr Gene Ther 2020; 20(4): 285-8.
[http://dx.doi.org/10.2174/1566523220999200820172829] [PMID: 32867652]
[42]
Ðokić JM, Tomić SZ, Čolić MJ. Cross-talk between mesenchymal stem/stromal cells and dendritic cells. Curr Stem Cell Res Ther 2016; 11(1): 51-65.
[http://dx.doi.org/10.2174/1574888X10666150904114035] [PMID: 26337378]
[43]
Ghosh T, Barik S, Bhuniya A, et al. Tumor-associated mesenchymal stem cells inhibit naïve T cell expansion by blocking cysteine export from dendritic cells. Int J Cancer 2016; 139(9): 2068-81.
[http://dx.doi.org/10.1002/ijc.30265] [PMID: 27405489]
[44]
Morrison TJ, Jackson MV, Cunningham EK, et al. Mesenchymal stromal cells modulate macrophages in clinically relevant lung injury models by extracellular vesicle mitochondrial transfer. Am J Respir Crit Care Med 2017; 196(10): 1275-86.
[http://dx.doi.org/10.1164/rccm.201701-0170OC] [PMID: 28598224]
[45]
Otsuka R, Seino K-I. Macrophage activation syndrome and COVID-19. Inflamm Regen 2020; 40: 19.
[http://dx.doi.org/10.1186/s41232-020-00131-w] [PMID: 32834892]
[46]
Schönrich G, Raftery MJ. Neutrophil extracellular traps go viral. Front Immunol 2016; 7: 366.
[http://dx.doi.org/10.3389/fimmu.2016.00366] [PMID: 27698656]
[47]
Spees JL, Lee RH, Gregory CA. Mechanisms of mesenchymal stem/stromal cell function. Stem Cell Res Ther 2016; 7(1): 125.
[http://dx.doi.org/10.1186/s13287-016-0363-7] [PMID: 27581859]
[48]
Kuraitis D, Giordano C, Ruel M, Musarò A, Suuronen EJ. Exploiting extracellular matrix-stem cell interactions: A review of natural materials for therapeutic muscle regeneration. Biomaterials 2012; 33(2): 428-43.
[http://dx.doi.org/10.1016/j.biomaterials.2011.09.078] [PMID: 22014942]
[49]
Hu S, Park J, Liu A, et al. Mesenchymal stem cell microvesicles restore protein permeability across primary cultures of injured human lung microvascular endothelial cells. Stem Cells Transl Med 2018; 7(8): 615-24.
[http://dx.doi.org/10.1002/sctm.17-0278] [PMID: 29737632]
[50]
Meng S-S, Guo F-M, Zhang X-W, et al. mTOR/STAT-3 pathway mediates mesenchymal stem cell-secreted hepatocyte growth factor protective effects against lipopolysaccharide-induced vascular endothelial barrier dysfunction and apoptosis. J Cell Biochem 2019; 120(3): 3637-50.
[http://dx.doi.org/10.1002/jcb.27642] [PMID: 30242894]
[51]
Medford ARL, Millar AB. Vascular endothelial growth factor (VEGF) in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): paradox or paradigm? Thorax 2006; 61(7): 621-6.
[http://dx.doi.org/10.1136/thx.2005.040204] [PMID: 16807391]
[52]
Chu X, Chen C, Chen C, Zhang J-S, Bellusci S, Li X. Evidence for lung repair and regeneration in humans: Key stem cells and therapeutic functions of fibroblast growth factors. Front Med 2020; 14(3): 262-72.
[http://dx.doi.org/10.1007/s11684-019-0717-5] [PMID: 31741137]
[53]
Caplan AI. Mesenchymal stem cells: Time to change the name! stem cells. Transl Med 2017; 6(6): 1445-51.
[http://dx.doi.org/10.1002/sctm.17-0051] [PMID: 28452204]
[54]
Bari E, Ferrarotti I, Saracino L, Perteghella S, Torre ML, Corsico AG. Mesenchymal stromal cell secretome for severe COVID-19 infections: Premises for the therapeutic use. Cells 2020; 9(4): 924.
[http://dx.doi.org/10.3390/cells9040924] [PMID: 32283815]
[55]
Crivelli B, Chlapanidas T, Perteghella S, et al. Mesenchymal stem/stromal cell extracellular vesicles: From active principle to next generation drug delivery system. J Control Release 2017; 262: 104-17.
[http://dx.doi.org/10.1016/j.jconrel.2017.07.023] [PMID: 28736264]
[56]
Ji F, Li L, Li Z, Jin Y, Liu W. Mesenchymal stem cells as a potential treatment for critically ill patients with coronavirus disease 2019. Stem Cells Transl Med 2020; 9(7): 813-4.
[http://dx.doi.org/10.1002/sctm.20-0083] [PMID: 32320535]
[57]
Sengupta V, Sengupta S, Lazo A, Woods P, Nolan A, Bremer N. Exosomes derived from bone marrow mesenchymal stem cells as treatment for severe COVID-19. Stem Cells Dev 2020; 29(12): 747-54.
[http://dx.doi.org/10.1089/scd.2020.0080] [PMID: 32380908]
[58]
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]
[59]
Zengin R, Beyaz O, Koc ES, et al. Mesenchymal stem cell treatment in a critically ill COVID-19 patient: A case report. Stem Cell Investig 2020; 7: 17.
[http://dx.doi.org/10.21037/sci-2020-024] [PMID: 33110915]
[60]
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]
[61]
Plava J, Cihova M, Burikova M, Matuskova M, Kucerova L, Miklikova S. Recent advances in understanding tumor stroma-mediated chemoresistance in breast cancer. Mol Cancer 2019; 18(1): 67.
[http://dx.doi.org/10.1186/s12943-019-0960-z] [PMID: 30927930]
[62]
Daverey A, Drain AP, Kidambi S. Physical intimacy of breast cancer cells with mesenchymal stem cells elicits trastuzumab resistance through src activation. Sci Rep 2015; 5: 13744.
[http://dx.doi.org/10.1038/srep13744] [PMID: 26345302]
[63]
Zheng C-X, Sui B-D, Liu N, et al. Adipose mesenchymal stem cells from osteoporotic donors preserve functionality and modulate systemic inflammatory microenvironment in osteoporotic cytotherapy. Sci Rep 2018; 8(1): 5215.
[http://dx.doi.org/10.1038/s41598-018-23098-8] [PMID: 29581449]
[64]
Xiao K, Hou F, Huang X, Li B, Qian ZR, Xie L. Mesenchymal stem cells: Current clinical progress in ARDS and COVID-19. Stem Cell Res Ther 2020; 11(1): 305.
[http://dx.doi.org/10.1186/s13287-020-01804-6] [PMID: 32698898]

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