PROSPECT OF STEM CELL THERAPY TO AVOID CYTOKINE STORM IN SEVERE COVID-19
Keywords:SARS-CoV-2, COVID-19, Mesenchymal stem cells, Immune-modulation, Anti-inflammation, Cytokine storm
Severe COVID-19 cases are mostly due to severe inflammatory reaction and cytokine storm, which may lead to multiple organ failure and death. Until recently, there is no proven effective treatment for severe COVID-19. Mesenchymal stem cells (MSCs) have anti-inflammatory and regenerative properties. Therefore, they are supposed to work on COVID-19, which has failed to recover using other treatments. Therefore, studies are needed to determine the best tissue source of MSCs, the dose, repeat, and route of administration. For this review, we searched various databases, i.e. Pubmed, Science Direct, Springer, and WHO website using keywords: “mesenchymal stem cells” and “COVID-19” at 7 May 2020, without time limits. Various clinical trials on the use of MSCs for COVID-19 were registered, and initial results were reported. Initial results were promising but should be interpreted cautiously, as one was a case report, another one was case series, and one was a preliminary study of seven treated patients compared to three controls, where the baseline conditions were unequal. Therefore, well design randomized clinical trials are needed to get more robust prove.
Ma J. Coronavirus: China’s first confirmed Covid-19 case traced back to November 17. South China Morning Post. Available from: https://www.scmp.com/news/china/society/article/3074991/coronavirus-chinas-first-confirmed-covid-19-case-traced-back. [Last accessed on 25 Mar 2020]
WHO. Emergencies preparedness, response. Pneumonia of unknown cause–China. WHO; 2020. Available from: https://www.who.int/csr/don/05-january-2020-pneumonia-of-unkown-cause-china/en/. [Last accessed on 25 Mar 2020]
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 Med 2020;382:727-33.
4WHO. Naming the coronavirus disease (Covid-19) and the virus that causes it. WHO; 2020. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/naming-the-coronavirus-disease-(covid-2019)-and-the-virus-that-causes-it. [Last accessed on 25 Mar 2020]
Hoffmann M, Kleine Weber H, Schroeder S, Kruger 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;181:271-80.
Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci 2020;12:8.
WHO. Virtual press conference on COVID-19. WHO; 2020. Available from: https://www.who.int/docs/default-source/coronaviruse/transcripts/who-audio-emergencies-coronavirus-press-conference-full-and-final-11mar2020.pdf?sfvrsn=cb432bb3_2. [Last accessed on 25 Mar 2020]
Kupferschmidt K, Cohen J. WHO launches global megatrial of the four most promising coronavirus treatments. Sciencemag; 2020. Available from: https://www.sciencemag.org/news/ 2020/03/who-launches-global-megatrial-four-most-promising-coronavirus-treatments. [Last accessed on 25 Mar 2020].
Li X, Geng M, Peng Y, Meng L, Lu S. Molecular immune pathogenesis and diagnosis of COVID-19. J Pharm Anal 2020;10:102-8.
Dominici M, Paolucci P, Conte P, Horwitz EM. Heterogeneity of multipotent mesenchymal stromal cells: from stromal cells to stem cells and vice versa. Transplantation 2009;87(9 Suppl):S36-42.
Dilogo IH, Mujadid F, Nurhayati RW, Kurniawan A. Evaluation of bone marrow-derived mesenchymal stem cell quality from patients with congenital pseudoarthrosis of the tibia. J Orthop Surg Res 2018;13:266.
Nofianti CE, Sari IN, Marlina, Novialdi, Pawitan JA. Temporary storage solution for adipose-derived mesenchymal stem cells. Stem Cell Investig 2018;5:19.
Smith JR, Pfeifer K, Petry F, Powell N, Delzeit J, Weiss ML. Standardizing umbilical cord mesenchymal stromal cells for translation to clinical use: a selection of GMP-compliant medium and a simplified isolation method. Stem Cells Int 2016;2016:6810980.
Fernandes TL, Cortez de Sant Anna JP, Frisene I, Gazarini JP, Gomes Pinheiro CC, Gomoll AH, et al. Systematic review of human dental pulp stem cells for cartilage regeneration. Tissue Eng Part B Rev 2020;26:1-12.
de Almeida DC, Ferreira MR, Franzen J, Weidner CI, Frobel J, Zenke M, et al. Epigenetic classification of human mesenchymal stromal cells. Stem Cell Reports 2016;6:168-75.
Dominici M, Le Blanc K, Mueller I, Slaper Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. International Society for Cellular Therapy position statement. Cytotherapy 2006;8:315–7.
Viswanathan S, Shi Y, Galipeau J, Krampera M, Leblanc K, Martin I, et al. Mesenchymal stem versus stromal cells: international society for cell and gene therapy (ISCT) mesenchymal stromal cell committee position statement on nomenclature. Cytotherapy 2019;21:1019-24.
Mendicino M, Fan Y, Griffin D, Gunter KC, Nichols K. Current state of U. S. food and drug administration regulation for cellular and gene therapy products: potential cures on the horizon. Cytotherapy 2019;21:699-724.
Mendicino M, Bailey AM, Wonnacott K, Puri RK, Bauer SR. MSC-based product characterization for clinical trials: an FDA perspective. Cell Stem Cell 2014;14:141-5.
Guadix JA, Lopez Beas J, Clares B, Soriano Ruiz JL, Zugaza JL, Galvez Martin P. Principal criteria for evaluating the quality, safety and efficacy of hMSC-based products in clinical practice: current approaches and challenges. Pharmaceutics 2019;11:pii:E552.
Gao F, Chiu SM, Motan DA, Zhang Z, Chen L, Ji HL, et al. Mesenchymal stem cells and immunomodulation: current status and future prospects. Cell Death Dis 2016;7:e2062.
Andreeva E, Bobyleva P, Gornostaeva A, Buravkova L. Interaction of multipotent mesenchymal stromal and immune cells: bidirectional effects. Cytotherapy 2017;19:1152-66.
Hodgkinson CP, Bareja A, Gomez JA, Dzau VJ. Emerging concepts in paracrine mechanisms in regenerative cardiovascular medicine and biology. Circ Res 2016;118:95-107.
Regmi S, Pathak S, Kim JO, Yong CS, Jeong JH. Mesenchymal stem cell therapy for the treatment of inflammatory diseases: challenges, opportunities, and future perspectives. Eur J Cell Biol 2019;98:151041.
Ciccocioppo R, Baumgart DC, Dos Santos CC, Galipeau J, Klersy C, Orlando G. Perspectives of the international society for cell and gene therapy gastrointestinal scientific committee on the intravenous use of mesenchymal stromal cells in inflammatory bowel disease (PeMeGi). Cytotherapy 2019;21:824-39.
Pawitan JA, Yang Z, Wu YN, Lee EH. Towards standardized stem cell therapy in type 2 diabetes mellitus: a systematic review. Curr Stem Cell Res Ther 2018;13:476-88.
Galipeau J. The mesenchymal stromal cells dilemma-does a negative phase III trial of random donor mesenchymal stromal cells in steroid-resistant graft-versus-host disease represent a death knell or a bump in the road? Cytotherapy 2013;15:2-8.
Srinivasan RC, Kannisto K, Strom SC, Gramignoli R. Evaluation of different routes of administration and biodistribution of human amnion epithelial cells in mice. Cytotherapy 2019;21:113-24.
Kabat M, Bobkov I, Kumar S, Grumet M. Trends in mesenchymal stem cell clinical trials 2004-2018: is efficacy optimal in a narrow dose range? Stem Cells Transl Med 2020;9:17–27.
Tian S, Hu W, Niu L, Liu H, Xu H, Xiao SY. Pulmonary pathology of early-phase 2019 novel coronavirus (COVID-19) pneumonia in two patients with lung cancer. J Thorac Oncol 2020;15:700-4.
Mattar P, Bieback K. Comparing the immunomodulatory properties of bone marrow, adipose tissue, and birth-associated tissue mesenchymal stromal cells. Front Immunol 2015;6:560.
WHO. International clinical trials registry platform (ICTRP). Available from: https://www.who.int/ictrp/en/ [Last accessed on 26 Mar 2020]
Leng Z, Zhu R, Hou W, Feng Y, Yang Y, Han Q, et al. Transplantation of ACE2-mesenchymal stem cells improves the outcome of patients with COVID-19 pneumonia. Aging Dis 2020;11:216-28.
Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708-20.
Xie J, Tong Z, Guan X, Du B, Qiu H. Clinical characteristics of patients who died of coronavirus disease 2019 in China. JAMA Netw Open 2020;3:e205619.
Jia HP, Look DC, Shi L, Hickey M, Pewe L, Netland J, et al. ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on the differentiation of human airway epithelia. J Virol 2005;79:14614‐21.
Zhao RC. Stem cell-based therapy for coronavirus disease in 2019. Stem Cells Dev 2020;29:679‐81.
Liang B, Chen J, Li T, Wu H, Yang W, Li Y, et al. Clinical remission of a critically ill COVID-19 patient treated by human umbilical cord mesenchymal stem cells. Chinaxiv: 202002:0084v1. Available from: http://www.chinaxiv.org/ abs/202002.00084. [Last accessed on 05 May 2020]
Terry M. Mesoblast’s stem cell therapy shows 83% survival in ventilator-dependent covid-19 patients. Biospace; 2020. Available from: https://www.biospace.com/article/mesoblast-ltd-s-stem-cell-therapy-shows-83-percent-survival-in-covid-19-patients/ [Last accessed on 27 Apr 2020]
Chang D, Mo G, Yuan X, Tao Y, Peng X, Wang FS, et al. Time kinetics of viral clearance and resolution of symptoms in novel coronavirus infection. Am J Respir Crit Care Med 2020;201:1150‐2.