Abstract
COVID-19 pandemic is a global health crisis of the 21st Century. There are currently no approved vaccines and no particular anti-viral treatment for coronavirus disease. As COVID-19 has a broad range of illnesses, it is necessary to find a safe and effective therapeutic method for COVID-19. An attractive approach for treating COVID-19 is cell therapy. Cell therapy aims to inject new and healthy stem cells into a patient’s body, to repair the damaged cells and tissues. Stem cell therapy is one of the most studied and important approaches in the treatment of COVID-19 these days. The significant clinical outcome was observed by the adoptive transfer of stem cells, specifically mesenchymal stem cells. This study reviews the characteristics of stem cells and clinical trials that have used stem cells in treating COVID-19.
Keywords: COVID-19, coronavirus, cell therapy, mesenchymal stem cells, clinical trials, β-CoV.
[1]
Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Me 2020; 328(8): 727-33.
[2]
Guo Y-R, Cao Q-D, Hong Z-S, Tan Y-Y, Chen S-D, Jin H-J, et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak–an update on the status. Military Medical Research 2020; 7(1): 1-10.
[3]
Yin Y, Wunderink RGJR. MERS, SARS and other coronaviruses as causes of pneumonia. 2018; 23(2): 130-7.
[4]
Guan W-j, Ni Z-y, Hu Y, Liang W-h, Ou C-q, He J-x, et al. Clinical characteristics of coronavirus disease 2019 in China. 2020; 382(18): 1708-20.
[http://dx.doi.org/10.1056/NEJMoa2002032]
[http://dx.doi.org/10.1056/NEJMoa2002032]
[5]
Golchin A, Seyedjafari E, Ardeshirylajimi AJSCR. Reports. Mesenchymal stem cell therapy for Covid-19: Present or future. Stem Cell Rev Rep 2020; 16(3): 427-33.
[6]
Kaye RJJPP. Overview of stem cell therapy for acute respiratory distress syndrome with focus on covid 19. Pain Physician 2020; 23(4S): S421-32.
[7]
Shetty AKJA. Mesenchymal stem cell infusion shows promise for combating Coronavirus (COVID-19)-induced pneumonia. Aging Dis 2020; 11(2): 462-64.
[8]
Basiri A, Pazhouhnia Z, Beheshtizadeh N, Hoseinpour M, Saghazadeh A, et al. Regenerative medicine in COVID-19 treatment: Real opportunities and range of promises 2020. Stem Cell Rev Rep 2021; 17(1): 163-75.
[9]
Yang X, Yu Y, Xu J, Shu H, Liu H, Wu Y, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study. Lancet Respir Med 2020; 8(5): 475-81.
[10]
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China 2020; 395(10223): 495-506.
[11]
van Boheemen S, de Graaf M, Lauber C, Bestebroer TM, Raj VS, Zaki AM, et al. Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans. mBio 2012; 3(6): e00473-12.
[http://dx.doi.org/10.1128/mBio.00473-12]
[http://dx.doi.org/10.1128/mBio.00473-12]
[12]
Raj VS, Mou H, Smits SL, Dekkers DH, Müller MA, Dijkman R, et al. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature 2013; 495(7440): 251-4.
[http://dx.doi.org/10.1038/nature12005]
[http://dx.doi.org/10.1038/nature12005]
[13]
Zou X, Chen K, Zou J, Han P, Hao J. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med 2020; 14(2): 185-92.
[14]
Chai X, Hu L, Zhang Y, Han W, Lu Z, Ke A, et al. Specific ACE2 expression in cholangiocytes may cause liver damage after 2019-nCoV infection. biorxiv 2020.
[15]
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181(2): 271-80.
[16]
Qin C, Zhou L, Hu Z, et al. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin Infect Dis 2020; 71(15): 762-8.
[17]
Shi Y, Tan M, Chen X, et al. Immunopathological characteristics of coronavirus disease 2019 cases in Guangzhou. Immunology 2020; 160(3): 261-8.
[18]
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]
[http://dx.doi.org/10.1016/S2213-2600(20)30076-X]
[19]
Abbaspanah B, Momeni M, Ebrahimi M. Advances in perinatal stem cells research: A precious cell source for clinical applications. Regen Med 2018; 13(5): 595-610.
[20]
Wang M, Yuan Q. Mesenchymal stem cell-based immunomodulation: Properties and clinical application. Stem Cells Int 2018; 2018: 3057624.
[21]
Caplan AI. Mesenchymal stem cells: Time to change the name! Stem Cells Transl Med 2017; 6(6): 1445-51.
[22]
Muguruma Y, Yahata T, Miyatake H, et al. Reconstitution of the functional human hematopoietic microenvironment derived from human mesenchymal stem cells in the murine bone marrow compartment. Blood 2006; 107(5): 1878-87.
[http://dx.doi.org/10.1182/blood-2005-06-2211]
[http://dx.doi.org/10.1182/blood-2005-06-2211]
[23]
Yong KW, Choi JR, Mohammadi M, Mitha AP, Sanati-Nezhad A, Sen AJSCI. Mesenchymal stem cell therapy for ischemic tissues. Stem Cells Int 2018; 2018: 8179075.
[http://dx.doi.org/10.1155/2018/8179075]
[http://dx.doi.org/10.1155/2018/8179075]
[24]
Mancuso P, Raman S, Glynn A, Barry F. Mesenchymal stem cell therapy for osteoarthritis: The critical role of the cell secretome 2. Front Bioeng Biotechnol 2019; 7: 9.
[25]
Shafei AES, Ali MA, Ghanem HG, et al. Mesenchymal stem cell therapy: A promising cell-based therapy for treatment of myocardial infarction. J Gene Med 2017; 19(12): e2995.
[http://dx.doi.org/10.1002/jgm.2995]
[http://dx.doi.org/10.1002/jgm.2995]
[26]
Wang L, Wang L, Cong X, et al. Human umbilical cord mesenchymal stem cell therapy for patients with active rheumatoid arthritis: Safety and efficacy. Stem Cells Dev 2013; 22(24): 3192-202.
[http://dx.doi.org/10.1089/scd.2013.0023] [PMID: 23941289]
[http://dx.doi.org/10.1089/scd.2013.0023] [PMID: 23941289]
[27]
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]
[http://dx.doi.org/10.1002/art.27548] [PMID: 20506343]
[28]
Hu J, Wang Y, Gong H, Yu C, Guo C, Wang F, et al. Long term effect and safety of Wharton's jelly-derived mesenchymal stem cells on type 2 diabetes. Exp Ther Med 2016; 12(3): 1857-66.
[http://dx.doi.org/10.3892/etm.2016.3544]
[http://dx.doi.org/10.3892/etm.2016.3544]
[29]
Zhang J, Lv S, Liu X, Song B, Shi L. Umbilical cord mesenchymal stem cell treatment for Crohn’s disease: a randomized controlled clinical trial. Gut Liver 2018; 12(1): 73-8.
[PMID: 28873511]
[PMID: 28873511]
[30]
Hou ZL, Liu Y, Mao X-H, et al. Transplantation of umbilical cord and bone marrow-derived mesenchymal stem cells in a patient with relapsing-remitting multiple sclerosis. Cell Adhes Migr 2013; 7(5): 404-7.
[PMID: 24192520]
[PMID: 24192520]
[31]
Xiang J-F. Effect of human umbilical cord mesenchymal stem cells on immune reconstruction of acute lymphoblastic leukemia children undergoing allogeneic hematopoietic stem cell transplantation. Chinese J Tissue Eng Res 2017; 21(29): 4679-84.
[32]
Reyhani S, Abbaspanah B, Mousavi SHJRM. Umbilical cord-derived mesenchymal stem cells in neurodegenerative disorders: From literature to clinical practice. Regen Med 2020; 15(4): 1561-78.
[33]
Prockop DJJSc. Concise review: Two negative feedback loops place mesenchymal stem/stromal cells at the center of early regulators of inflammation. 2013; 31(10): 2042-6.
[34]
Wang Y, Chen X, Cao W. Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications. Nat Immunol 2014; 15(11): 1009-16.
[35]
Kean TJ, Lin P, Caplan AI. Dennis JEJSci. MSCs: Delivery routes and engraftment, cell-targeting strategies, and immune modulation. Stem Cells Int 2013; 2013: 732742.
[36]
Aboalola D, Han VKJSCI. Different effects of insulin-like growth Factor-1 and insulin-like growth Factor-2 on myogenic differentiation of human mesenchymal stem cells. Stem Cells Int 2017; 2017: 8286248.
[http://dx.doi.org/10.1155/2017/8286248]
[http://dx.doi.org/10.1155/2017/8286248]
[37]
Bernardo ME. Mesenchymal stromal cells: Sensors and switchers of inflammation. Cell Stem Cell 2013; 13(4): 392-402.
[38]
Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts AI, et al. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell 2008; 2(2): 141-50.
[http://dx.doi.org/10.1016/j.stem.2007.11.014]
[http://dx.doi.org/10.1016/j.stem.2007.11.014]
[39]
Zhu Y, Chen X, Yang X. Stem cells in lung repair and regeneration: Current applications and future promise J Cell Physiol 2018; 233(10): 6414-24.
[40]
Bari E, Ferrarotti I, Torre ML, Corsico AG. Mesenchymal stem/stromal cell secretome for lung regeneration: The long way through “pharmaceuticalization” for the best
formulation J Control Release 2019; 309: 11-24.
[41]
Ayala-Cuellar AP, Kang J-H, Jeung E-B, Choi K-CJB. Roles of mesenchymal stem cells in tissue regeneration and immunomodulation Biomol Ther (Seoul) 2019; 27(1): 25.
[42]
Zanoni M, Cortesi M, Zamagni A. The role of mesenchymal stem cells in radiation-induced lung fibrosis 2019; 20(16): 3876.
[43]
Savukinas UB, Enes SR, Sjöland AA. Concise review: The Bystander Effect: Mesenchymal stem cell-mediated lung repair. Stem Cells 2016; 34(6): 1437-44.
[44]
Leng Z, Zhu R, Hou W, et al. Transplantation of ACE2-mesenchymal stem cells improves the outcome of patients with COVID-19 pneumonia. Stem Cells 2020; 11(2): 216-8.
[http://dx.doi.org/10.14336/AD.2020.0228]
[http://dx.doi.org/10.14336/AD.2020.0228]
[45]
Lee JW, Krasnodembskaya A, McKenna DH, Song Y, Abbott J. Therapeutic effects of human mesenchymal stem cells in ex vivo human lungs injured with live bacteria Am J Respir Crit Care Med 2013; 187(7): 751-60.
[46]
Nagamura-Inoue T. He HJWjosc. Umbilical cord-derived mesenchymal stem cells: their advantages and potential clinical utility World J Stem Cells 2014; 6(2): 195.
[47]
Liang B, Chen J, Li T, Wu H, Yang W, Li Y. Clinical remission of a critically ill COVID-19 patient treated by human umbilical cord mesenchymal stem cells. Medicine (Baltimore) 2020; 31: e21429.
[http://dx.doi.org/10.1097/MD.0000000000021429]
[http://dx.doi.org/10.1097/MD.0000000000021429]
[48]
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): 1-7.
[49]
Tian X, Woll PS, Morris JK, Linehan JL, Kaufman DS. Hematopoietic engraftment of human embryonic stem cell‐derived cells is regulated by recipient innate immunity Stem Cells 2006; 24(5): 1370-80.
[50]
Lund RD, Wang S, Klimanskaya I, Holmes T, Ramos-Kelsey R, Lu B. Human embryonic stem cell–derived cells rescue visual function in dystrophic RCS rats Cloning Stem Cells 2006; 8(3): 189-99.
[http://dx.doi.org/10.1089/clo.2006.8.189]
[http://dx.doi.org/10.1089/clo.2006.8.189]
[51]
Hess DC, Sila CA, Furlan AJ, Wechsler LR, Switzer JA. A double-blind placebo-controlled clinical evaluation of MultiStem for the treatment of ischemic stroke Int J Stroke 2014; 9(3): 381-6.
[52]
Mousavi SH, Zarrabi M, Abroun S, Ahmadipanah M. Umbilical cord blood quality and quantity: Collection up to transplantation. Asian J Transfus Sci 2019; 13(2): 79.
[53]
Copelan EAJNEJoM. Hematopoietic stem-cell transplantation. N Engl J Med 2006; 354(17): 1813-26.
[54]
Zhao YJCdr. Stem cell educator therapy and induction of immune balance. Curr Diab Rep 2012; 12(5): 517-23.
[55]
Hinrichs CS. Restifo NP. Reassessing target antigens for adoptive T-cell therapy. Nat Biotechnol 2013; 31(11): 999-1008.
[56]
Soo Y, Cheng Y, Wong R, Hui D, Lee C, Tsang K. Retrospective comparison of convalescent plasma with continuing high-dose methylprednisolone treatment in SARS patients. Clin Microbiol Infect 2004; 10(7): 676-8.
[http://dx.doi.org/10.1111/j.1469-0691.2004.00956.x]
[http://dx.doi.org/10.1111/j.1469-0691.2004.00956.x]
[57]
Chen L, Xiong J, Bao L Shi. Convalescent plasma as a potential therapy for COVID-19. Lancet Infect Dis 2020; 20(4): 398-400.
[http://dx.doi.org/10.1016/S1473-3099(20)30141-9]
[http://dx.doi.org/10.1016/S1473-3099(20)30141-9]
[58]
Ye M, Fu D, Ren Y, Wang F, Wang D, Zhang F. Treatment with convalescent plasma for COVID‐19 patients in Wuhan. J Med Virol 2020; 10: 1890-901.
[59]
Abolghasemi H, Eshghi P, Cheraghali AM, Fooladi AAI, Moghaddam FB, Imanizadeh S. Clinical efficacy of convalescent plasma for treatment of COVID-19 infections: Results of a multicenter clinical study. Transfus Apher Sci 2020; 102875.
[60]
Casadevall A, Joyner MJ. SARS-CoV-2 viral load and antibody responses: The case for convalescent plasma therapy. J Clin Invest 2020; 130(10): 5112-4.
[61]
Hu Y, Yin ETS, Yang Y, Wu H, Wei G, Su J. CAR T-cell treatment during the COVID-19, pandemic: management strategies and challenges. Curr Res Transl Med 2020; 68(3): 111-8.
[62]
Miliotou AN. Papadopoulou LCJCpb. CAR T-cell therapy: A new era in cancer immunotherapy. Curr Pharm Biotechnol 19(1): 5-18.
[63]
Zhang J, Basher F. Wu. NKG2D ligands in tumor immunity: Two sides of a coin. Front Immunol 2015; 6: 97.
[64]
Ferlazzo G, Pack M, Thomas D, Paludan C, Schmid D, Strowig T. Distinct roles of IL-12 and IL-15 in human natural killer cell activation by dendritic cells from secondary lymphoid organs. Proc Natl Acad Sci USA 2004; 101(47): 16606-1.
[http://dx.doi.org/10.1073/pnas.0407522101]
[http://dx.doi.org/10.1073/pnas.0407522101]
[65]
Andoniou C, Coudert JD, Degli-Esposti MJ. Cross talk between NK cells and adaptive immune cells. 2008;38(11):2938-42. Eur J Immunol 2008; 38(11): 2938-42.
[66]
Schuster IS, Coudert JD, Andoniou CE. Natural regulators”: NK cells as modulators of T cell immunity Front Immunol 2016; 235.
[67]
Jamieson A, Diefenbach A, McMahon C, Xiong N, Carlyle J, Raulet DJI. The role of the NKG2D immunoreceptor in immune cell activation and natural killing. Immunity 2004; 20(6): 799.
[http://dx.doi.org/10.1016/j.immuni.2004.05.003]
[http://dx.doi.org/10.1016/j.immuni.2004.05.003]
[68]
Haanen JB, Cerundolo VJC. NKG2A, a new kid on the immune checkpoint block Cell 2018; 175(7): 1720-2.
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