Will Mesenchymal Stem Cell Therapy Be Effective In COVID-19?

  • Srinivas kalai Pharm D
  • M Senthil Department of Pharmacy Practice, Department of Pharmaceutics, J.K.K.Nattraja College of Pharmacy, Kumarapalayam-638183, Tamil Nadu, India https://orcid.org/0000-0002-8741-362X
  • R Sambath Kumar Department of Pharmacy Practice, Department of Pharmaceutics, J.K.K.Nattraja College of Pharmacy, Kumarapalayam-638183, Tamil Nadu, India https://orcid.org/0000-0002-8741-362X
  • R Kameshwaran Department of Pharmacy Practice, Department of Pharmaceutics, J.K.K.Nattraja College of Pharmacy, Kumarapalayam-638183, Tamil Nadu, India

Abstract

Background: The World Health Organization (WHO) reports that the outbreak of the deadly virus had been noted almost in all the countries worldwide. Newly no standard therapies are available to combat the situation and this remains the major challenge for healthcare professionals to provide effective treatment against the life-threatening condition. A potential regenerative medicine method using the infusion of stem cells for the treatment of lung disorders has been reported. This review attempted to explore the immunomodulatory characteristics of Mesenchymal Stem Cells (MSCs) and how these properties make them beneficial for the treatment of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) patients.


Objectives: To study the effect of Mesenchymal Stem Cell therapy in treating COVID-19.


Methodology: A literature search was conducted to identify recent research relating to the review's goal of analyzing the relevance of stem cells in battling SARS-CoV-2.


Results: The MSCs settle in the lungs intravenously to enhance the pulmonary microenvironment, minimize immune system over-activation, and encourage regeneration of damaged lung tissues. Its therapeutic properties like immune response inhibition play a major role in combating viruses. The avoidance of cytokine storm is the most important stage in COVID-19 therapy. Their potent immunomodulatory properties have positive effects in avoiding or attenuating the cytokine storm and assisting in the regeneration of injured lung tissues/other organs.


Conclusion: Intravenous human Umbilical Cord-Mesenchymal Stem Cell therapy (hUC-MSC) transplantation is a safe and effective technique that may be used as a restoration and prioritized therapeutic option for treating severe COVID-19.


Keywords: Covid-19, human Umbilical Cord-Mesenchymal Stem Cell therapy (huc-msc), Immune system.

Keywords: Covid-19, human Umbilical Cord-Mesenchymal Stem Cell therapy (huc-msc), Immune system

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Author Biographies

M Senthil, Department of Pharmacy Practice, Department of Pharmaceutics, J.K.K.Nattraja College of Pharmacy, Kumarapalayam-638183, Tamil Nadu, India

Department of Pharmacy Practice, Department of Pharmaceutics, J.K.K.Nattraja College of Pharmacy, Kumarapalayam-638183, Tamil Nadu, India

R Sambath Kumar, Department of Pharmacy Practice, Department of Pharmaceutics, J.K.K.Nattraja College of Pharmacy, Kumarapalayam-638183, Tamil Nadu, India

Department of Pharmacy Practice, Department of Pharmaceutics, J.K.K.Nattraja College of Pharmacy, Kumarapalayam-638183, Tamil Nadu, India

R Kameshwaran, Department of Pharmacy Practice, Department of Pharmaceutics, J.K.K.Nattraja College of Pharmacy, Kumarapalayam-638183, Tamil Nadu, India

Department of Pharmacy Practice, Department of Pharmaceutics, J.K.K.Nattraja College of Pharmacy, Kumarapalayam-638183, Tamil Nadu, India

References

1. Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020; 382:1708–20.10.doi:1056/NEJMoa2002032
2. Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020; 395:565-74. https://doi.org/10.1016/ S0140-6736(20)30251-8
3. Banerjee A, Kulcsar K, Misra V, et al. Bats and coronaviruses. Viruses. 2019; 11(1):41.doi:10.3390/v11010041
4. Yang D, Leibowitz JL.The structure and functions of coronavirus genomic 3' and 5' ends. Virus Res. 2015; 206:120-33. doi:10.1016/j.virusres.2015.02.025
5. Kotton, DN. Next-generation regeneration. American Journal of Respiratory and Critical Care Medicine.2012; 185(12):1255– 1260. doi:https://www.atsjournals.org/doi/full/10.1164/rccm.201202-0228PP
6. Weiss DJ. Concise review: Current status of stem cells and regenerative medicine in lung biology and diseases. Stem Cells.2014; 32(1):16–25.doi:10.1002/stem.1506
7. Fernanda F, Patricia RM. Stem-Cell extracellular vesicles and lung repair. Stem Cell. 2017; 4:1–11. doi:10.21037/sci.2017.09.02
8. Li F, Li W, Farzan M, et al. Structural biology: Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science. 2005; 309(5742):1864–1868.doi: https://doi.org/10.1126/science.1116480
9. World Health Organization. WHO Director-General’s opening remarks at the media briefing on COVID-19 - 11 March 2020. Retrieved March 14, 2020. Available at: https://www.who.int/dg/speeches/detail/ who-director-general-s-opening-remarks-at-the-media-briefing-oncovid-19%2D%2D-11-march-2020
10. Ji Y, Ma Z, Peppelenbosch MP, et al. Potential association between COVID-19 mortality and health-care resource availability. The Lancet Glob. 2020; 8(4):e480. doi: https://doi.org/ 10.1016/S2214-109X(20)30068-1
11. Baud D, Qi X, Nielsen-Saines K, et al. Real estimates of mortality following COVID19 infection. The Lancet Infect Dis. 2020; 20(7):773. doi: https://doi.org/ 10.1016/S1473-3099(20)30195-X
12. Petros RA, DeSimone, JM. Strategies in the design of nanoparticles for therapeutic applications. Nat. Rev. Drug Discov. 2010; 9: 615–627. doi:10.1038/nrd2591
13. Chauhan G, Madou M. J, Kalra S, et al. Nanotechnology for COVID-19: therapeutics and vaccine research. ACS Nano. 2020; 14 (7): 7760–7782. doi:10.1021/acsnano.0c04006
14. Banchereau J, Steinman, R. M. Dendritic cells and the control of immunity. Nature. 1998; 392:245–252. doi:10.1038/32588
15. Mainardes RM, Diedrich C. The potential role of nanomedicine on COVID-19 therapeutics. Therap. Deliv.2020; 11:7–9. doi:10.4155/tde-2020-0069
16. Campos ER, Pereira AE, de Oliveira JL, et al. How can nanotechnology help to combat COVID-19? opportunities and urgent need. J. Nanobiotechnol. 2020; 18: 1–23. doi:10.1186/s12951-020-00685-4
17. Zhang Q, Honko A, Zhou J, et al. Cellular nanosponges inhibit SARS-CoV-2 infectivity. Nano Lett. 2020; 20: 5570–5574. doi:10.1021/acs.nanolett.0c02278
18. Cavezzi A., Troiani E, Corrao S. COVID-19: hemoglobin, iron, and hypoxia beyond inflammation. A narrative review. Clin. Pract. 2020; 10: 1271. doi:10. 4081/cp.2020.1271
19. Destache CJ, Belgum T, Christensen K, et al. Combination antiretroviral drugs in PLGA nanoparticle for HIV-1. BMC Infect. Dis. 2009; 9: 198. doi:10.1186/1471-2334-9-198
20. Joffre OP, Segura E, Savina A, et al. Cross-presentation by dendritic cells. Nat. Rev. Immunol.2012; 12: 557–569. doi:10.1038/nri3254
21. Witika BA, Makoni PA, Mweetwa LL, et al. Nano-biomimetic drug delivery vehicles: potential approaches for COVID-19 treatment. Molecules. 2020; 25: 5952. doi:10.3390/molecules25245952
22. Bajada S, Mazakova I, Richardson JB, et al. Updates on stem cells and their application in regenerative medicine. J Tissue Eng Regen Med. 2008; 2(4):169–83. doi:10.1002/term.83
23. Lee KD, Kuo TK, Whang-Peng J, et al. In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology. 2004; 40(6):1275–1284. doi: 10.1002/hep.20469
24. Ratajczak MZ, Marycz K, Poniewierska-Baran A, et al. Very small embryonic-like stem cells as a novel developmental concept and the hierarchy of the stem cell compartment. Adv Med Sci. 2014; 59(2):273–280. doi: 10.1016/j.advms.2014.08.001
25. Yang J, Jia Z. Cell-based therapy in lung regenerative medicine. Regenerative Medicine Research. 2014; 2:1–7. doi: 10.1186/2050-490X-2-7
26. Behnke J, Kremer S, Shahzad T,et al. MSC based therapies-New perspectives for the injured lung. J Clin Med. 2020; 3(9):682. doi: 10.3390/jcm9030682
27. Weiss DJ. Mesenchymal stem cells for lung repair and regeneration. Stem cells in the respiratory system (pp. 25–42). New York: Springer Science & Business Media.
28. Ding DC, Shyu WC, Lin SZ, et al.Current con-cepts in adult stem cell therapy for stroke. Curr. Med. Chem. 2006;13(29):3565–3574. doi: 10.2174/092986706779026237
29. Ding DC, Shyu WC, Lin SZ, et al. The role of endothelial progenitor cells in ischemic cerebral and heart diseases. Cell Transplant. 2007; 16(3):273–284. doi: 10.3727/00000000778346477
30. Potten CS, Loeffler M. Stem cells: Attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. Development. 1990; 110(4):1001–1020. PMID: 2100251
31. Dennis JE, Carbillet JP, Caplan AI, et al. The STRO-1+ marrow cell population is multipotential. Cells Tissues Organs. 2002; 170(2–3):73–82. doi: 10.1159/000046182
32. Torensma R, Jansen JA, Figdor CG. Ceramic hydroxyapatite coating on titanium implants drives selective bone marrow stromal cell adhesion. Clin. Oral Implants Res. 2003; 14(5):569–577. doi: 10.1034/j.1600-0501.2003.00949.x
33. Gronthos S, Graves SE, Ohta SJ, et al. The STRO-1+ fraction of adult human bone marrow contains the osteogenic precursors. Blood.1994; 84(12):4164–4173. PMID: 7994030
34. Gronthos S, Zannettino AC, Hay SJ, et al. Molecular and cellular characterisation of highly purified stromal stem cells derived from human bone marrow. J. Cell Sci. 2003; 116(9):1827–1835. doi: 10.1242/jcs.00369
35. Golchin A, Farahany, TZ, Khojasteh A, et al. The clinical trials of Mesenchymal stem cell therapy in skin diseases: An update and concise review. Curr Stem Cell Res Ther. 2019; 14(1), 22–33. https://doi.org/10. 2174/1574888x13666180913123424
36. Khoury M, Cuenca J, Cruz FF, et al. Current status of cell-based therapies for respiratory virus infections: Applicability to COVID-19. Eur Respir J. 2020; 55(6): 2000858. doi: https://doi.org/10. 1183/13993003.00858-2020
37. Frauwirth KA, Thompson CB. Activation and inhibition of lymphocytes by Costimulation. J Clin Invest. 2002; 109: 295–299. doi: 10.1172/JCI14941
38. Glennie S, Soeiro I, Dyson PJ, et al. Bone marrow Mesenchymal stem cells induce division arrest anergy of activated T cells. Blood. 2005; 105: 2821–2827. doi: 10.1182/blood-2004-09-3696
39. Rawlings JS, Rosler KM, Harrison DA. The JAK/ STAT signaling pathway. J Cell Sci. 2004; 117: 1281– 1283. doi: 10.1242/jcs.00963
40. Meisel R, Zibert A, Laryea M, et al. Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase–mediated tryptophan degradation. Blood. 2004; 103(12):4619–4621. doi: 10.1182/blood-2003-11-3909
41. Mbongue J, Nicholas D, Torrez T, et al. The role of indoleamine 2, 3-dioxygenase in immune suppression and autoimmunity. Vaccines. 2015; 3:703–729. doi: https://doi.org/10.3390/vaccines3030703
42. Haddad R, Saldanha-Araujo F. Mechanisms of T-cell immunosuppression by mesenchymal stromal cells: What do we know so far? Bio Med Research International.2014:1–14. doi: https://doi.org/10.1155/2014/216806
43. Stagg J. Immune regulation by mesenchymal stem cells: Two sides to the coin. Tissue Antigens. 2007; 69(1):1–9. doi: 10.1111/j.1399-0039.2006.00739.x
44. Briones J, Novelli S, Sierra J. T-cell costimulatory molecules in acute-graft-versus host disease: Therapeutic implications. Bone Marrow Res. 2011; 2011: 976793. doi: 10.1155/2011/976793
45. Najar M, Raicevic G, Kazan HF, at al. Immune-related antigens, surface molecules and regulatory factors in human-derived mesenchymal stromal cells: The expression and impact of inflammatory priming. Stem Cell Rev Rep. 2012;8(4): 1188–1198. doi: 10.1007/s12015-012-9408-1
46. Saldanha-Araujo F, Ferreira FIS, Palma PV, et al. Mesenchymal Stromal cells up-regulate CD39 and increase adenosine production to suppress activated T-lymphocytes. Stem Cell Res. 2011; 7(1): 66–74. doi: 10.1016/j.scr.2011.04.001
47. Pevsner-Fischer M, Morad V, Cohen-Sfady M, et al. Toll-like receptors and their ligands control mesenchymal stem cell functions. Blood. 2007; 109(4): 1422–1432. doi: 10.1182/blood-2006-06-028704
48. Opitz CA, Litzenburger UM, Lutz C, et al. Toll-like receptor engagement enhances the immunosuppressive properties of human bone marrow-derived mesenchymal stem cells by inducing indoleamine-2,3-dioxygenase-1 via interferon-β and protein kinase R. Stem Cells. 2009; 27(4): 909–919. doi: 10.1002/stem.7
49. Bunnell BA, Betancourt AM, Sullivan DE. New concepts on the immune modulation mediated by mesenchymal stem cells. Stem Cell Res Ther. 2010; 1(5):34. doi: 10.1186/scrt34
50. Raicevic G, Rouas R, Najar M, et al. Inflammation modifies the pattern and the function of toll-like receptors expressed by human mesenchymal stromal cells. Hum Immunol. 2010; 71(3): 235–244. doi: 10.1016/j.humimm.2009.12.005
51. Rasmusson I. Immune modulation by mesenchymal stem cells. Exp Cell Res. 2006; 312(12): 2169–2179. doi: 10.1016/j.yexcr.2006.03.019
52. Gao F, Chiu SM, Motan DAL, et al. Mesenchymal stem cells and immunomodulation: Current status and future prospects. Cell Death Dis. 2016; 7(1): e2062–e2062. doi: 10.1038/cddis.2015.327
53. Bailey CC, Zhong G, Huang IC, et al. IFITM-family proteins: The Cell’s first line of antiviral defense. Annu Rev Virol. 2014; 1(1):261–283. doi: https://doi.org/10. 1146/annurev-virology-031413-085537
54. Schoggins JW. Interferon-stimulated genes: What do they all do? Annu Rev Virol. 2019; 6(1): 567–584. doi: https:// doi.org/10.1146/annurev-virology-092818-015756
55. Wu X, Dao Thi VL, Huang Y, et al. Intrinsic Immunity Shapes Viral Resistance of Stem Cells. Cell. 2018; 172(3):423–438.e25. doi: https://doi. org/10.1016/j.cell.2017.11.018
56. Kane M, Zang TM, Rihn SJ, et al. Identification of interferon-stimulated genes with antiretroviral activity. Cell Host Microbe. 2016; 20(3): 392–405. doi: https://doi.org/10.1016/j.chom.2016.08.005
57. McIntyre LA., Moher D, Fergusson DA, et al. Efficacy of mesenchymal stromal cell therapy for acute lung injury in preclinical animal models: A systematic review. PLoS One. 2016; 11(1). doi: https://doi.org/10.1371/ journal.pone.0147170
58. Chan MCW, Kuok DIT, Leung C, et al. Human mesenchymal stromal cells reduce influenza a H5N1-associated acute lung injury in vitro and in vivo. Proceedings of the National Academy of Sciences of the United States of America. 2016; 113(13): 3621–3626. doi: https://doi.org/10.1073/pnas.1601911113
59. Bing L, Junhui C, Tao L, et al. Clinical remission of a critically ill COVID-19 patient treated by human umbilical cord. ChinaXiv. 2020; 99(31): e21429. doi: https://doi.org/10.12074/ 202002.00084
60. Darwish I, Mubareka S, Liles WC. Immunomodulatory therapy for severe influenza. Expert Rev Anti-infect Ther. 2011; 9: 807–822. doi: 10.1586/eri.11.56
61. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 Novel Coronavirus in Wuhan, China. The Lancet. 2020; 395:497–506. doi: 10.1016/S0140-6736(20)30183-5
62. 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):1061-1069. doi: 10.1001/jama.2020.1585
63. 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):216-228. doi: 10.14336/AD.2020.0228
64. Shetty AK. Mesenchymal stem cell infusion shows promise for combating coronavirus (COVID-19) induced pneumonia. Aging Dis. 2020; 11(2): 462-464. doi: 10.14336/AD.2020.0301
65. Chen J, Hu C, Chen L, et al. Clinical Study of Mesenchymal Stem Cell Treatment for Acute Respiratory Distress Syndrome Induced by Epidemic Influenza A (H7N9) Infection: A Hint for COVID-19 Treatment. Engineering. 2020; 6(10): 1153–1161 doi: https://doi. org/10.1016/j.eng.2020.02.006
66. Ma N, Gai H, Mei J, et al. Bone marrow mesenchymal stem cells can differentiate into type II alveolar epithelial cells in vitro. Cell Biol Int. 2011; 35(12):1261–1266. doi: 10.1042/CBI20110026
67. Leeman KT, Pessina P, Lee J, et al. Mesenchymal stem cells increase alveolar differentiation in lung progenitor organoid cultures. Sci Rep. 2019; 9: 1–10. doi: 10.1038/s41598-019-42819-1
68. Hu D, Zhu C, Ai L, et al. Genomic characterization and infectivity of a novel SARS-like coronavirus in Chinese bats. Emerg Microbes Infect. 2018; 7: 1–10. doi: 10.1038/s41426-018-0155-5
69. Lei Shu, Changming Niu , Ruyou Li., et al, Treatment of severe COVID-19 with human umbilical cord mesenchymal stem cells. Stem Cell Research & Therapy. 2020; 11:361. doi: https://doi.org/10.1186/s13287-020-01875-5
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kalai S, Senthil M, Sambath Kumar R, Kameshwaran R. Will Mesenchymal Stem Cell Therapy Be Effective In COVID-19?. JDDT [Internet]. 15Nov.2021 [cited 1Dec.2021];11(6):281-5. Available from: https://jddtonline.info/index.php/jddt/article/view/5143