Mesenchymal Stem Cell as a Successful Therapy for COVID-19 Patient: Systematic Review

Rahmah Qisti Nandina(1), Kartini Eriani(2), Cynthia Wahyu Asrizal(3), Al Azhar(4),


(1) Department of Biology, Faculty of Mathematics and Natural Science, Universitas Syiah Kuala, Indonesia
(2) Department of Biology, Faculty of Mathematics and Natural Science, Universitas Syiah Kuala, Indonesia
(3) Department of Physiology, Faculty of Medicine, Universitas Syiah Kuala, Indonesia
(4) Departement of Biochemistry, Faculty of Veterinary Medicine, Universitas Syiah Kuala, Indonesia

Abstract

COVID-19 has been declared a pandemic and continues to spread, leading to health and economic problems and economic burdens worldwide. COVID-19 symptoms are similar to the flu and, in severely infected patients, emerge as an acute respiratory syndrome (ARDS), pulmonary fibrosis, edema, and even organ failure. These are due to an imbalanced immune response with a more severe effect than the virus attack. However, no specific medications and treatments are available in dealing with the COVID-19. Hence, mesenchymal stem cell (MSC) treatment is proposed as one therapeutic approach. The MSCs can produce growth factors and immune protective cytokines that could fight viral infection and are proven to help endothelial cell repair. These capabilities are expected to help resist viruses and tissue repair in a patient body. MSC is believed to prevent acute respiratory infections, the most dangerous stage of COVID-19 pathogenesis. In this study, we collect some literature, reviewing and summarizing them so that we believe that MSC could be an approach to cure COVID-19 patients and improve their responses to the virus. This article reviews the use of mesenchymal stem cells as a potential therapy for COVID-19, and this information can also be used as basic information for developing a stem-cell-based therapy, especially for treating COVID-19.

Keywords

COVID-19, Mesenchymal Stem Cells, MSCs therapy

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References

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Zhao, Q., Ren, H., & Han, Z. (2016). Mesenchymal stem cells : Immunomodulatory capability and clinical potential in immune diseases. Journal of Cellular Immunotherapy, 2(1), 3–20. https://doi.org/10.1016/j.jocit.2014.12.001

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Chen, J., Hu, C., Chen, L., Tang, L., Zhu, Y., Xu, X., Chen, L., Gao, H., Lu, X., Yu, L., Dai, X., Xiang, C., & Li, L. (2020). 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, 6(10), 1153–1161. https://doi.org/10.1016/j.en g.2020. 02.006

Galipeau, J., & Sensébé, L. (2018). Mesenchymal stromal cells: clinical challenges and therapeutic opportunities. Cell Stem Cell., 22(6), 824–833. https://doi.org/10.1016/j.stem .2018.05.004.Mesenchymal

Galleu, A., Riffo-Vasquez, Y., Trento, C., Lomas, C., Dolcetti, L., Cheung, T. S., Von Bonin, M., Barbieri, L., Halai, K., Ward, S., Weng, L., Chakraverty, R., Lombardi, G., Watt, F. M., Orchard, K., Marks, D. I., Apperley, J., Bornhauser, M., Walczak, H., … Dazzi, F. (2017). Apoptosis in mesenchymal stromal cells induces in vivo recipient-mediated immunomodulation. Science Translational Medicine, 9(416), 1–12. https://doi.org/10. 1126/scitranslmed.aam7828

Ge, Q., Zhang, H., Hou, J., Wan, L., Cheng, W., Wang, X., Dong, D., Chen, C., Xia, J., Guo, J., Chen, X., & Wu, X. (2018). VEGF secreted by Mesenchymal stem cells mediates the differentiation of endothelial progenitor cells into endothelial cells via paracrine mechanisms. Molecular Medicine Reports, 17(1), 1667–1675. https://doi.org/10.3892/mm r.2017.8059

Golchin, A., & Farahany, T. Z. (2019). Biological Products: Cellular Therapy and FDA Approved Products. Stem Cell Reviews and Reports, 15(2), 166–175. https://doi.org/10.10 07/s12015 -018-9866-1

Guo, Y.-R., Cao, Q.-D., Hong, Z.-S., Tan, Y.-Y., Che, S.-D., Jin, H.-J., Tan, K.-S., Wang, D.-Y., & Yan1, Y. (2020). The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak – an update on the status. Military Medical Research, 7, 1–10. https://doi.org/10.1093/eurheartj/ehaa396

Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., Schiergens, T. S., Herrler, G., Wu, N. H., Nitsche, A., Müller, M. A., Drosten, C., & Pöhlmann, S. (2020). SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell, 181(2), 271-280.e8. https://doi. org/10.1016/j.cell.2020.02.052

Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X., Cheng, Z., Yu, T., Xia, J., Wei, Y., Wu, W., Xie, X., Yin, W., Li, H., Liu, M., … Cao, B. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet, 395(10223), 497–506. https://doi.org/ 10.1016/S0140-6736(20)30183-5

Kirchdoerfer, R. N., Cottrell, C. A., Wang, N., Pallesen, J., Yassine, H. M., Turner, H. L., Corbett, K. S., Graham, B. S., McLellan, J. S., & Ward, A. B. (2016). Pre-fusion structure of a human coronavirus spike protein. Nature, 531(7592), 118–121. https://doi.org/10.1038/n ature17200

Leng, Z., Zhu, R., Hou, W., Feng, Y., Yang, Y., Han, Q., Meng, F., Du, D., Wang, S., Fan, J., Wang, W., Deng, L., Shi, H., Li, H., Hu, Z., Zhang, F., Gao, J., Liu, H., Li, X., … Yang, B. (2020). Transplantation of ACE2 - Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia. Aging and Disease, 11(2), 216–228.http://dx.doi.org/10.14336/AD.2020.0228Liang, B., Chen, J., Li, T., Wu, H., Yang, W., Li, Y., Li, J., Yu, C., Nie, F., Ma, Z., Yang, M., Xiao, M., Nie, P., Gao, Y., Qian, C., & Hu, M. (2020). Clinical remission of a critically ill COVID-19 patient treated by human umbilical cord mesenchymal stem cells: A case report. Medicine, 99(31), 1–6. https://doi.org/10. 1097/MD.0000000000021429

Lu, R., Zhao, X., Li, J., Niu, P., Yang, B., Wu, H., Wang, W., Song, H., Huang, B., Zhu, N., Bi, Y., Ma, X., Zhan, F., Wang, L., Hu, T., Zhou, H., Hu, Z., Zhou, W., Zhao, L., … Tan, W. (2020). Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The Lancet, 395(10224), 565–574. https://doi.org/10.1016/S0140-736(20)30251-8

Meftahi, G. H., Jangravi, Z., Sahraei, H., & Bahari, Z. (2020). The possible pathophysiology mechanism of cytokine storm in elderly adults with COVID-19 infection: the contribution of “inflame-aging.” Inflammation Research, 69(9), 825–839. https://doi.org/10.1007/s0001 1 -020-01372-8

Metcalfe, S. M. (2020). Mesenchymal stem cells and management of COVID-19 pneumonia. Medicine in Drug Discovery, 5, 100019. https://doi.org/10.1016/j.medidd.2020.100019

Putra, A., Widyatmoko, A., Ibrahim, S., Amansyah, F., Amansyah, F., Berlian, M. A., Retnaningsih, R., Pasongka, Z., Sari, F. E., Rachmad, B., & Moll, G. (2021). Case series of the first three severe COVID-19 patients treated with the secretome of hypoxia-mesenchymal stem cells in Indonesia [ version 3 ; peer review : 1 ap proved , 1 approved with reservations ]. 1–18.

Raza, S. S., Seth, P., & Khan, M. A. (2021). ‘ Primed ’ Mesenchymal Stem Cells : a Potential Novel Therapeutic for COVID19 Patients. Stem Cell Reviews and Reports, 17, 153–162. https://doi.org/10.1007/s12015-020099990%0 A‘Primed’

Robb, C. T., Regan, K. H., Dorward, D. A., & Rossi, A. G. (2016). Key mechanisms governing resolution of lung inflammation. Seminars in Immunopathology, 38(4), 425–448. https://doi. org/10.1007/s00281-016-0560-6

Rothan, H. A., & Byrareddy, S. N. (2020). The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. Journal of Autoimmunity, 109(February), 102433. https:// doi.org/10.1016/j.jaut.2020.102433

Samavati, L., & Uhal, B. D. (2020). ACE2, Much More Than Just a Receptor for SARS-COV-2. Frontiers in Cellular and Infection Microbiology, 10(June), 1–9. https://doi.org/ 10.3389/fcimb.2020.00317

Shang, J., Ye, G., Shi, K., Wan, Y., Luo, C., Aihara, H., Geng, Q., Auerbach, A., & Li, F. (2020). Structural basis of receptor recognition by SARS-CoV-2. Nature, 581(February), 221–22 4. https://doi.org/10.1038/s41586-020-2179-y

Shu, L., Niu, C., Li, R., Huang, T., Wang, Y., Huang, M., Ji, N., & Zheng, Y. (2020). Treatment of severe COVID-19 with human umbilical cord mesenchymal stem cells. Stem Cell Research & Therapy, 11, 1–11.

Sinclair, K., Yerkovich, S. T., & Chambers, D. C. (2013). Mesenchymal stem cells and the lung. Respirology, 18(3), 397–411. https://doi.org/ 10.1111/resp.12050

Tang, L., Jiang, Y., Zhu, M., Chen, L., Zhou, X., Zhou, C., Ye, P., Jiang, W., Qu, J., Xiang, C., & Li, L. (2020). Clinical study using mesenchymal stem cells for the treatment of patients with severe COVID-19. 14(5), 664–673.

Tay, M. Z., Poh, C. M., Rénia, L., MacAry, P. A., & Ng, L. F. P. (2020). The trinity of COVID-19: immunity, inflammation and intervention. Nature Reviews Immunology, 20(6), 363–374. https://doi.org/10.1038/s41577-020-0311-8

Wang, Y., Han, Z. B., Ma, J., Zuo, C., Geng, J., Gong, W., Sun, Y., Li, H., Wang, B., Zhang, L., He, Y., & Han, Z. C. (2012). A toxicity study of multiple-administration human umbilical cord mesenchymal stem cells in cynomolgus monkeys. Stem Cells and Development, 21(9), 1401–1408. https://doi. org/10.1089/scd.2011.0 441

WHO. (2020). Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19). In The WHO-China Joint Mission on Coronavirus Disease 2019 (Issue February). https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf

Xu, Z., Shi, L., Wang, Y., Zhang, J., Huang, L., Zhang, C., Liu, S., Zhao, P., Liu, H., Zhu, L., Tai, Y., Bai, C., Gao, T., Song, J., Xia, P., Dong, J., Zhao, J., & Wang, F.-S. (2020). Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med., 8(feb 25), 420–422. https://doi.org/10.1016/S2213-2600(20)30076-X

Yan R, Zhang Y, Li Y, Xia L, Guo Y, & Zhou Q. (2020). Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science, 367(March), 1444–1448.

Zhao, Q., Ren, H., & Han, Z. (2016). Mesenchymal stem cells : Immunomodulatory capability and clinical potential in immune diseases. Journal

of Cellular Immunotherapy, 2(1), 3–20. https://doi.org/10.1016/j.jocit.2014.12.001

Zhou, P., Yang, X. Lou, Wang, X. G., Hu, B., Zhang, L., Zhang, W., Si, H. R., Zhu, Y., Li, B., Huang, C. L., Chen, H. D., Chen, J., Luo, Y., Guo, H., Jiang, R. Di, Liu, M. Q., Chen, Y., Shen, X. R., Wang, X., … Shi, Z. L. (2020). A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 579(7798), 270–273. https://doi.org/10.1038/ s41586-020-2012-7

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