ISSN (print) 1726-9806     ISSN (online) 1818-474X
No. 1 (2023), COVID-19 DISEASE
No. 1 (2023)
COVID-19 DISEASE

The use of mesenchymal stem cells in the treatment of severe forms of new coronavirus infection COVID-19: a prospective observational study

Published 31.01.2023
Aleksandr M. Dzyadzko
Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology, Minsk, Belarus
https://orcid.org/0000-0003-1965-1850
S. I. Krivenko
Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology, Minsk, Belarus
https://orcid.org/0000-0002-6813-4465
A. V. Syradouey
Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology, Minsk, Belarus
https://orcid.org/0000-0003-2504-0618
N. I. Dedylya
Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology, Minsk, Belarus
https://orcid.org/0000-0001-9807-2093
P. S. Prylutski
Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology, Minsk, Belarus
https://orcid.org/0000-0002-5274-2714
E. A. Prymakova
Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology, Minsk, Belarus
https://orcid.org/0000-0002-3011-2287
A. A. Symanovich
Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology, Minsk, Belarus
https://orcid.org/0000-0003-1521-1620
E. A. Nazarova
Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology, Minsk, Belarus
https://orcid.org/0000-0001-7147-4834
K. H. Petrovskaya
Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology, Minsk, Belarus
https://orcid.org/0000-0002-0966-7456
V. V. Smolnikova
Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology, Minsk, Belarus
https://orcid.org/0000-0001-5947-8285
I. A. Romanova
Minsk Scientific and Practical Center for Surgery, Transplantology and Hematology, Minsk, Belarus
https://orcid.org/0000-0001-6577-9738
#2023-1
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Keywords

coronavirus infection
COVID-19
SARS-CoV-2
mesenchymal stem cells
cytokine storm

How to Cite

Dzyadzko A.M., Krivenko S.I., Syradouey A.V., Dedylya N.I., Prylutski P.S., Prymakova E.A., Symanovich A.A., Nazarova E.A., Petrovskaya K.H., Smolnikova V.V., Romanova I.A. The use of mesenchymal stem cells in the treatment of severe forms of new coronavirus infection COVID-19: a prospective observational study. Annals of Critical Care. 2023;(1):71–82. doi:10.21320/1818-474X-2023-1-71-82.
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Abstract

INTRODUCTION: One of the promising treatments for COVID-19 aimed at correcting the immune response and reducing the level of pro-inflammatory cytokines is the use of mesenchymal stem cells (MSCs). There is evidence that MSCs, due to various mechanisms, are able to suppress the cytokine storm in patients with COVID-19. Thus, the use of MSCs can contribute to the suppression of inflammation and the regulation of immune homeostasis in patients with severe COVID-19. OBJECTIVE: Evaluation of the effect of mesenchymal stem cell (MSC) therapy on the course of severe forms of novel coronavirus infection, accompanied by “cytokine storm”. MATERIALS AND METHODS: A prospective single-center study included 39 patients treated for coronavirus infection on the basis of the intensive care unit and, after randomization, randomly divided into control (n = 16) and study groups (n = 23). An assessment of clinical, laboratory parameters in both groups and a cytokine profile in the study group was carried out. Outcomes were compared, the incidence of complications and clinical and laboratory parameters in both groups, and the cytokine profile in the study group. RESULTS: The use of MSCs in patients with severe forms of COVID-19 affected the outcomes of the disease, the duration of stay on mechanical ventilation, the course of acute respiratory distress syndrome (ARDS) (an increase in the oxygenation index in patients of the study group by 5, 7 days from administration in comparison with the control group). CONCLUSIONS: In patients treated with MSCs, there was a significant decrease in a number of pro-inflammatory cytokines.

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References

  1. Ramasamy S., Subbian S. Critical Determinants of Cytokine Storm and Type I Interferon Response in COVID-19 Pathogenesis. Clinical microbiology reviews. 2021; 34(3). DOI: 10.1128/CMR.00299-20
  2. Tsatsakis A., Calina D., Falzone L., et al. SARS-CoV-2 pathophysiology and its clinical implications: An integrative overview of the pharmacotherapeutic management of COVID-19. Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association. 2020; 146: 111769. DOI: 10.1016/j.fct.2020.111769
  3. Wang J., Jiang M., Chen X., et al. Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: Review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts. J Leukoc Biol. 2020; 108(1): 17–41. DOI: 10.1002/JLB.3COVR0520-272R
  4. Fajgenhaum D.C., June C.H. Cytokine Storm. N Engl J Med. 2020; 383(23): 2255–73. DOI: 10.1056/NEJMra2026131
  5. Zhu R., Yan T., Feng Y., et al. Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms. Cell Res. 2021; 31(12): 1244–62. DOI: 10.1038/s41422-021-00573-y
  6. Waterman R.S., Tomchuck S.L., Henkle S.L., et al. A new mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an immunosuppressive MSC2 phenotype. PLoS One. 2010; 5: e10088. DOI: 10.1371/journal.pone.0010088
  7. Elgaz S., Kuci Z., Kuci S., et al. Clinical use of mesenchymal stromal cells in the treatment of acute graft-versus-host disease. Transfus Med Hemother. 2019; 46: 27–34. DOI: 10.1159/000496809
  8. Coelho A., Alvites R.D., Branquinho M.V., et al. Mesenchymal stem cells (MSCs) as a potential therapeutic strategy in COVID-19 patients: literature research. Front Cell Dev Biol. 2020; 8: 602647. DOI: 10.3389/fcell.2020.602647
  9. Yen B.L., Yen M.L., Wang L.T., et al. Current status of mesenchymal stem cell therapy for immune/inflammatory lung disorders: gleaning insights for possible use in COVID-19. Stem Cells Transl Med. 2020; 9: 1163–73. DOI: 10.1002/sctm.20-0186
  10. Barros I., Silva A., de Almeida L.P., et al. Mesenchymal stromal cells to fight SARS-CoV-2: Taking advantage of a pleiotropic therapy. Cytokine Growth Factor Rev. 2021; 58: 114–33. DOI: 10.1016/j.cytogfr.2020.12.002
  11. Musial C., Gorska-Ponikowska M. Medical progress: stem cells as a new therapeutic strategy for COVID-19. Stem Cell Res. 2021; 52: 102239. DOI: 10.1016/j.scr.2021.102239
  12. Su Y., Guo H., Liu Q. Effects of mesenchymal stromal cell-derived extracellular vesicles in acute respiratory distress syndrome (ARDS): current understanding and future perspectives. J Leukoc Biol. 2021; 110: 27–38. DOI: 10.1002/JLB.3MR0321-545RR
  13. 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. DOI: 10.14336/AD.2020.0228
  14. 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.
  15. Kaffash Farkhad N., Reihani H., Sedaghat A., et al. Are mesenchymal stem cells able to manage cytokine storm in COVID-19 patients? A review of recent studies. Regen Ther. 2021: 152–60. DOI: 10.1016/j.reth.2021.05.007
  16. Vincent J.L., Moreno R., Takala J., et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996 ;22(7): 707–10. DOI: 10.1007/BF01709751
  17. Knaus W.A., Draper E.A., Wagner D.P., et al. APACHE II: a severity of disease classification system. Crit Care Med.1985; 13(10): 818–29.
  18. The ARDS Definition Task Force. Acute Respiratory Distress Syndrome: The Berlin Definition. JAMA. 2012; 307(23): 2526–33. DOI: 10.1001/jama.2012.5669
  19. Qin C., Zhou L., Hu Z., et al. Dysregulation of Immune Response in Patients with Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 2020; 71(15): 762–68. DOI: 10.1093/cid/ciaa248
  20. Tan L., Wang Q., Zhang D., et al. Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study. Signal Tranduct Target Ther. 2020; 5: 33.
  21. Wan S.X., Yi Q.J., Fan S.B., et al. Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP). MedRxiv. 2020. DOI: 10.1101/2020.02.10.20021832. 2020.02.10.20021832
  22. Matthay M.A., Calfee C.S., Zhuo H., et al. Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): a randomised phase 2a safety trial. The Lancet Respiratory Medicine. 2019; 7(2): 154–62. DOI: 10.1016/s2213-2600(18)30418-1
  23. Goudouris E.S. Laboratory diagnosis of COVID-19. Jornal de Pediatria. 2020. DOI: 10.1016/j.jped.2020.08.001
  24. Bivona G., Agnello L., Ciacco M. Biomarkers for Prognosis and Treatment Response in COVID-19 Patients. Ann Lab Med. 2021; 41(6): 540–8. DOI: 10/3343/alm.2021.41.6.540
  25. 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; 6(30): 100454. DOI: 10.1016/j.eclinm.2020.100454
  26. Blaber S.P., Webster R.A., Hill C.J., et al. Analysis of in vitro secretion profiles from adipose-derived cell populations. J Transl Med. 2012; 10: 172. DOI: 10.1186/1479-5876-10-172
  27. Kallmeyer K., Pepper M.S. Homing properties of mesenchymal stromal cells. Expert Opin Biol Ther. 2015; 15: 477–9. DOI: 10.1517/14712598.2015.997204
  28. Copcu H.E. Potential using of fat-derived stromal cells in the treatment of active disease, and also, in both pre- and post-periods in COVID-19. Aging Dis. 2020; 11: 730–6. DOI: 10.14336/AD.2020.0621
  29. Jeyaraman M., Ranjan R., Kumar R., et al. Cellular therapy: shafts of light emerging for COVID-19. Stem Cell Investig. 2020; 7: 11. DOI: 10.21037/sci-2020-022
  30. Juárez-Navarro K.J., Padilla-Camberos E., Díaz N.F., et al. Human Mesenchymal stem cells: the present alternative for high-incidence diseases, even SARS-Cov-2. Stem Cells Int. 2020: 8892189. DOI: 10.1155/2020/8892189
  31. Rogers C.J., Harman R.J., Bunnell B.A., et al. Rationale for the clinical use of adipose-derived mesenchymal stem cells for COVID-19 patients. J Transl Med. 2020; 18: 203. DOI: 10.1186/s12967-020-02380-2
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