Generic placeholder image

Current Stem Cell Research & Therapy


ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Review Article

The Promise of Mesenchymal Stem Cells Therapy for Acute Respiratory Distress Syndrome Caused by COVID-19

Author(s): Jundong Gu, Qinjun Zhao, Zhibo Han and Zhongchao Han*

Volume 16, Issue 3, 2021

Published on: 29 July, 2020

Page: [277 - 285] Pages: 9

DOI: 10.2174/1574888X15999200729161539

Price: $65


The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since Dec 2019, known as COVID-19 or 19-nCoV, has led to a major concern of the potential for not only an epidemic but a pandemic in China and now it seems to be a public health problem all over the world. The general mortality rate of the COVID-19 was about 3%. However, the mortality risk seems to be a significant increase in elderly and cases with chronic disease, who are more likely to develop into acute respiratory distress syndrome (ARDS). There still lacks effective methods for ARDS of COVID-19 patients and the prognosis was poor. Mesenchymal Stem Cells (MSCs) based treatment has the advantage of targeting numerous pathophysiological components of ARDS by secreting a series of cell factors, exerting anti-inflammatory, antioxidative, immunomodulatory, antiapoptotic, and proangiogenic effects, resulting in significant structural and functional recovery following ARDS in various preclinical models. Recently, pilot clinical studies indicated MSCs based therapy was promise in treatment of ARDS caused by SARS-CoV-2. However, little is known about MSCs therapy for ARDS caused by COVID-19.

Keywords: Mesenchymal stem cell, SARS-CoV-2, COVID-19, ARDS, antiapoptotic, proangiogenic.

Lancet T. Emerging understandings of 2019-nCoV. Lancet 2020; 395(10221): 311.
[] [PMID: 31986259]
Lu CW, Liu XF, Jia ZF. 2019-nCoV transmission through the ocular surface must not be ignored. Lancet 2020; 395(10224)e39
[] [PMID: 32035510]
Wang FS, Zhang C. What to do next to control the 2019-nCoV epidemic? Lancet 2020; 395(10222): 391-3.
[] [PMID: 32035533]
Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may be at least partially responsible for the respiratory failure of COVID-19 patients. J Med Virol 2020; 92: 552-5.
[] [PMID: 32104915]
Meo SA, Alhowikan AM, Al-Khlaiwi T, et al. Novel coronavirus 2019-nCoV: Prevalence, biological and clinical characteristics comparison with SARS-CoV and MERS-CoV. Eur Rev Med Pharmacol Sci 2020; 24(4): 2012-9.
[PMID: 32141570 ]
Liu J, Zheng X, Tong Q, et al. Overlapping and discrete aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARS-CoV, MERS-CoV, and 2019-nCoV. J Med Virol 2020; 92(5): 491-4.
[] [PMID: 32056249]
Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in china: Summary of a report of 72 314 cases from the chinese center for disease control and prevention. JAMA 2020; 323(13): 1239-42.
[] [PMID: 32091533]
Xu XW, Wu XX, Jiang XG, et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: Retrospective case series. BMJ 2020; 368: m606.
[] [PMID: 32075786]
Guan WJ, Ni ZY, Hu Y, et al. China medical treatment expert group for Covid-19. Clinical characteristics of coronavirus disease 2019 in china. N Engl J Med 2020; 382(18): 1708-20.
[] [PMID: 32109013]
Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet 2020; 395(10223): 507-13.
[] [PMID: 32007143]
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395(10223): 497-506.
[] [PMID: 31986264]
Chousterman BG, Swirski FK, Weber GF. Cytokine storm and sepsis disease pathogenesis. Semin Immunopathol 2017; 39(5): 517-28.
[] [PMID: 28555385]
Behrens EM, Koretzky GA. Review: Cytokine storm syndrome: Looking toward the precision medicine era. Arthritis Rheumatol 2017; 69(6): 1135-43.
[] [PMID: 28217930]
Gerlach H. Agents to reduce cytokine storm. F1000 Res 2016; 5: 2909.
[] [PMID: 28105327]
Meduri GU, Schwingshackl A, Hermans G. Prolonged glucocorticoid treatment in ARDS: Impact on intensive care unit-acquired weakness. Front Pediatr 2016; 4: 69.
[] [PMID: 27532030]
Meduri GU, Yates CR. Systemic inflammation-associated glucocorticoid resistance and outcome of ARDS. Ann N Y Acad Sci 2004; 1024: 24-53.
[] [PMID: 15265772]
Peck TJ, Hibbert KA. Recent advances in the understanding and management of ARDS. F1000 Res 2019; 8: 8.
[] [PMID: 31824644]
Dries DJ. ARDS from syndrome to disease-treatment strategies. Air Med J 2019; 38(2): 64-7.
[] [PMID: 30898284]
Huang X, Xiu H, Zhang S, Zhang G. The role of macrophages in the pathogenesis of ALI/ARDS. Mediators Inflamm 2018; 20181264913
[] [PMID: 29950923]
Nash G. Pathology of ARDS. West J Med 1979; 130(3): 220-2.
[PMID: 425504]
Bhadade RR, de Souza RA, Harde MJ, Khot A. Clinical characteristics and outcomes of patients with acute lung injury and ARDS. J Postgrad Med 2011; 57(4): 286-90.
[] [PMID: 22120856]
Máca J, Jor O, Holub M, et al. Past and present ARDS mortality rates: A systematic review. Respir Care 2017; 62(1): 113-22.
[] [PMID: 27803355]
Andrews PL, Shiber JR, Jaruga-Killeen E, et al. Early application of airway pressure release ventilation may reduce mortality in high-risk trauma patients: A systematic review of observational trauma ARDS literature. J Trauma Acute Care Surg 2013; 75(4): 635-41.
[] [PMID: 24064877]
Xu L, Gong Y, Wang B, et al. Randomized trial of autologous bone marrow mesenchymal stem cells transplantation for hepatitis B virus cirrhosis: Regulation of Treg/Th17 cells. J Gastroenterol Hepatol 2014; 29(8): 1620-8.
[] [PMID: 24942592]
Jang YO, Kim YJ, Baik SK, et al. Histological improvement following administration of autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis: A pilot study. Liver Int 2014; 34(1): 33-41.
[] [PMID: 23782511]
Zhang Z, Lin H, Shi M, et al. Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients. J Gastroenterol Hepatol 2012; 27(Suppl. 2): 112-20.
[] [PMID: 22320928]
Riordan NH, Morales I, Fernández G, et al. Clinical feasibility of umbilical cord tissue-derived mesenchymal stem cells in the treatment of multiple sclerosis. J Transl Med 2018; 16(1): 57.
[] [PMID: 29523171]
Dahbour S, Jamali F, Alhattab D, et al. Mesenchymal stem cells and conditioned media in the treatment of multiple sclerosis patients: Clinical, ophthalmological and radiological assessments of safety and efficacy. CNS Neurosci Ther 2017; 23(11): 866-74.
[] [PMID: 28961381]
Llufriu S, Sepúlveda M, Blanco Y, et al. Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis. PLoS One 2014; 9(12)e113936
[] [PMID: 25436769]
Deng D, Zhang P, Guo Y, Lim TO. A randomised double-blind, placebo-controlled trial of allogeneic umbilical cord-derived mesenchymal stem cell for lupus nephritis. Ann Rheum Dis 2017; 76(8): 1436-9.
[] [PMID: 28478399]
Gu F, Wang D, Zhang H, et al. Allogeneic mesenchymal stem cell transplantation for lupus nephritis patients refractory to conventional therapy. Clin Rheumatol 2014; 33(11): 1611-9.
[] [PMID: 25119864]
Luo W, Yu H, Gou J,et al. Clinical pathology of critical patient with novel coronavirus pneumonia (COVID-19). Preprints 2020; p. 2020: 020407.
Bian Xiu-Wu. The COVID-19 Pathology Team, Autopsy of COVID-19 victims in China, National Science Review, nwaa123.
Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS. J Virol 2020; 94(7): e00127-20.
[] [PMID: 31996437]
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.
[] [PMID: 32085846]
Passos-Silva DG, Verano-Braga T, Santos RA. Angiotensin-(1-7): beyond the cardio-renal actions. Clin Sci (Lond) 2013; 124(7): 443-56.
[] [PMID: 23249272]
Celec P. Nuclear factor kappa B-molecular biomedicine: The next generation. Biomed Pharmacother 2004; 58(6-7): 365-71.
[] [PMID: 15271418]
Kuba K, Imai Y, Rao S, Jiang C, Penninger JM. Lessons from SARS: Control of acute lung failure by the SARS receptor ACE2. J Mol Med (Berl) 2006; 84(10): 814-20.
[] [PMID: 16988814]
Vlahos R, Stambas J, Selemidis S. Suppressing production of reactive oxygen species (ROS) for influenza A virus therapy. Trends Pharmacol Sci 2012; 33(1): 3-8.
[] [PMID: 21962460]
Forman HJ, Torres M. Reactive oxygen species and cell signaling: Respiratory burst in macrophage signaling. Am J Respir Crit Care Med 2002; 166(12 Pt 2): S4-8.
[] [PMID: 12471082]
Wang W, Han ZC. Heterogeneity of Human Mesenchymal Stromal/Stem Cells. Adv Exp Med Biol 2019; 1123: 165-77.
[] [PMID: 31016600]
Tao H, Han Z, Han ZC, Li Z. Proangiogenic features of mesenchymal stem cells and their therapeutic applications. Stem Cells Int 2016; 20161314709
[] [PMID: 26880933]
Liu M, Han ZC. Mesenchymal stem cells: Biology and clinical potential in type 1 diabetes therapy. J Cell Mol Med 2008; 12(4): 1155-68.
[] [PMID: 18298656]
Chen X, Wang S, Cao W. Mesenchymal stem cell-mediated immunomodulation in cell therapy of neurodegenerative diseases. Cell Immunol 2018; 326: 8-14.
[] [PMID: 28778534]
Su Y, Shi S, Liu Y. Immunomodulation regulates mesenchymal stem cell-based bone regeneration. Oral Dis 2014; 20(7): 633-6.
[] [PMID: 24725095]
Fierabracci A, Del Fattore A, Luciano R, Muraca M, Teti A, Muraca M. Recent advances in mesenchymal stem cell immunomodulation: The role of microvesicles. Cell Transplant 2015; 24(2): 133-49.
[] [PMID: 24268069]
Uccelli A, de Rosbo NK. The immunomodulatory function of mesenchymal stem cells: Mode of action and pathways. Ann N Y Acad Sci 2015; 1351: 114-26.
[] [PMID: 26152292]
Jin HJ, Bae YK, Kim M, et al. Comparative analysis of human mesenchymal stem cells from bone marrow, adipose tissue, and umbilical cord blood as sources of cell therapy. Int J Mol Sci 2013; 14(9): 17986-8001.
[] [PMID: 24005862]
Fayyad-Kazan H, Faour WH, Badran B, Lagneaux L, Najar M. The immunomodulatory properties of human bone marrow-derived mesenchymal stromal cells are defined according to multiple immunobiological criteria. Inflamm Res 2016; 65(6): 501-10.
[] [PMID: 26956767]
Liu G, Wang L, Pang T, et al. Umbilical cord-derived mesenchymal stem cells regulate thymic epithelial cell development and function in Foxn1(-/-) mice. Cell Mol Immunol 2014; 11(3): 275-84.
[] [PMID: 24561455]
Zhou YZ, Cheng Z, Wu Y, et al. Mesenchymal stem cell-derived conditioned medium attenuate angiotensin II-induced aortic aneurysm growth by modulating macrophage polarization. J Cell Mol Med 2019; 23(12): 8233-45.
[] [PMID: 31583844]
Lo Sicco C, Reverberi D, Balbi C, et al. Mesenchymal stem cell-derived extracellular vesicles as mediators of anti-inflammatory effects: Endorsement of macrophage polarization. Stem Cells Transl Med 2017; 6(3): 1018-28.
[] [PMID: 28186708]
Lu Z, Chang W, Meng S, et al. Mesenchymal stem cells induce dendritic cell immune tolerance via paracrine hepatocyte growth factor to alleviate acute lung injury. Stem Cell Res Ther 2019; 10(1): 372.
[] [PMID: 31801626]
Fu X, Liu G, Halim A, Ju Y, Luo Q, Song AG. Mesenchymal stem cell migration and tissue repair. Cells 2019; 8(8): 784.
[] [PMID: 31357692]
Zipori D. Mesenchymal stem cells: Harnessing cell plasticity to tissue and organ repair. Blood Cells Mol Dis 2004; 33(3): 211-5.
[] [PMID: 15528133]
Rojas M, Xu J, Woods CR, et al. Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol 2005; 33(2): 145-52.
[] [PMID: 15891110]
Rojas M, Cárdenes N, Kocyildirim E, et al. Human adult bone marrow-derived stem cells decrease severity of lipopolysaccharide-induced acute respiratory distress syndrome in sheep. Stem Cell Res Ther 2014; 5(2): 42.
[] [PMID: 24670268]
Lee JW, Fang X, Gupta N, Serikov V, Matthay MA. Allogeneic human mesenchymal stem cells for treatment of E. coli endotoxin-induced acute lung injury in the ex vivo perfused human lung. Proc Natl Acad Sci USA 2009; 106(38): 16357-62.
[] [PMID: 19721001]
Valcz G, Krenács T, Sipos F, et al. The role of the bone marrow derived mesenchymal stem cells in colonic epithelial regeneration. Pathol Oncol Res 2011; 17(1): 11-6.
[] [PMID: 20405350]
Ortiz LA, Gambelli F, McBride C, et al. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci USA 2003; 100(14): 8407-11.
[] [PMID: 12815096]
Harting MT, Jimenez F, Xue H, et al. Intravenous mesenchymal stem cell therapy for traumatic brain injury. J Neurosurg 2009; 110(6): 1189-97.
[] [PMID: 19301973]
Gupta N, Su X, Popov B, Lee JW, Serikov V, Matthay MA. Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J Immunol 2007; 179(3): 1855-63.
[] [PMID: 17641052]
Xu J, Woods CR, Mora AL, et al. Prevention of endotoxin-induced systemic response by bone marrow-derived mesenchymal stem cells in mice. Am J Physiol Lung Cell Mol Physiol 2007; 293(1): L131-41.
[] [PMID: 17416739]
Mei SH, Haitsma JJ, Dos Santos CC, et al. Mesenchymal stem cells reduce inflammation while enhancing bacterial clearance and improving survival in sepsis. Am J Respir Crit Care Med 2010; 182(8): 1047-57.
[] [PMID: 20558630]
Németh K, Leelahavanichkul A, Yuen PS, et al. Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med 2009; 15(1): 42-9.
[] [PMID: 19098906]
Krasnodembskaya A, Song Y, Fang X, et al. Antibacterial effect of human mesenchymal stem cells is mediated in part from secretion of the antimicrobial peptide LL-37. Stem Cells 2010; 28(12): 2229-38.
[] [PMID: 20945332]
Zheng G, Huang L, Tong H, et al. Treatment of acute respiratory distress syndrome with allogeneic adipose-derived mesenchymal stem cells: A randomized, placebo-controlled pilot study. Respir Res 2014; 15: 39.
[] [PMID: 24708472]
Wilson JG, Liu KD, Zhuo H, et al. Mesenchymal stem (stromal) cells for treatment of ARDS: A phase 1 clinical trial. Lancet Respir Med 2015; 3(1): 24-32.
[] [PMID: 25529339]
Liang Bing, Junhui Chen, Tao Li, et al. Clinical remission of a critically ill COVID-19 patient treated by human umbilical cord mesenchymal stem cells. Medicine 2020; 99(31): e21429.
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.
[] [PMID: 32257537]
Matthay MA, Calfee CS, 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. Lancet Respir Med 2019; 7(2): 154-62.
[] [PMID: 30455077]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy