MSC-Based Cell Therapy for COVID-19-Associated ARDS and Classical ARDS: Comparative Perspectives

Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory distress in adults. Lancet. 1967;2(7511):319–23.

Article  CAS  PubMed  Google Scholar 

Matthay MA, Zemans RL, Zimmerman GA, Arabi YM, Beitler JR, Mercat A, et al. Acute respiratory distress syndrome. Nat Rev Dis Primers. 2019;5(1):18.

Article  PubMed  PubMed Central  Google Scholar 

Yadav H, Thompson BT, Gajic O. Fifty years of research in ARDS. Is acute respiratory distress syndrome a preventable disease? Am J Respir Crit Care Med. 2017;195(6):725–36.

Calfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA, et al. Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials. Lancet Respir Med. 2014;2(8):611–20.

Article  PubMed  PubMed Central  Google Scholar 

•• Wilson JG, Calfee CS. ARDS subphenotypes: understanding a heterogeneous syndrome. Crit Care. 2020;24(1):102. This study summarizes the current knowledge of ARDS subphenotypes.

Article  PubMed  PubMed Central  Google Scholar 

Reilly JP, Calfee CS, Christie JD. Acute respiratory distress syndrome phenotypes. Semin Respir Crit Care Med. 2019;40(1):19–30.

Article  PubMed  PubMed Central  Google Scholar 

Grasselli G, Calfee CS, Camporota L, Poole D, Amato MBP, Antonelli M, et al. ESICM guidelines on acute respiratory distress syndrome: definition, phenotyping and respiratory support strategies. Intensive Care Med. 2023;49(7):727–59.

Article  PubMed  PubMed Central  Google Scholar 

Sinha P, Kerchberger VE, Willmore A, Chambers J, Zhuo H, Abbott J, et al. Identifying molecular phenotypes in sepsis: an analysis of two prospective observational cohorts and secondary analysis of two randomised controlled trials. Lancet Respir Med. 2023.

Moore AR, Pienkos SM, Sinha P, Guan J, O’Kane CM, Levitt JE, et al. Elevated plasma interleukin-18 identifies high-risk acute respiratory distress syndrome patients not distinguished by prior latent class analyses using traditional inflammatory cytokines: a retrospective analysis of two randomized clinical trials. Crit Care Med. 2023.

Zheng G, Huang L, Tong H, Shu Q, Hu Y, Ge M, 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.

Article  PubMed  PubMed Central  Google Scholar 

Wilson JG, Liu KD, Zhuo H, Caballero L, McMillan M, Fang X, et al. Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial. Lancet Respir Med. 2015;3(1):24–32.

Article  PubMed  Google Scholar 

Matthay MA, Calfee CS, Zhuo H, Thompson BT, Wilson JG, Levitt JE, 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.

Article  PubMed  Google Scholar 

Simonson OE, Mougiakakos D, Heldring N, Bassi G, Johansson HJ, Dalen M, et al. In vivo effects of mesenchymal stromal cells in two patients with severe acute respiratory distress syndrome. Stem Cells Transl Med. 2015;4(10):1199–213.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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(8):727–33.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan. China Lancet. 2020;395(10223):497–506.

Article  CAS  PubMed  Google Scholar 

Beloncle FM. Is COVID-19 different from other causes of acute respiratory distress syndrome? J Intensive Med. 2023;3(3):212–9.

Article  PubMed  PubMed Central  Google Scholar 

Zhu Y, Sharma L, Chang D. Pathophysiology and clinical management of coronavirus disease (COVID-19): a mini-review. Front Immunol. 2023;14:1116131.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Leisman DE, Deutschman CS, Legrand M. Facing COVID-19 in the ICU: vascular dysfunction, thrombosis, and dysregulated inflammation. Intensive Care Med. 2020;46(6):1105–8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

•• Couto PS, Al-Arawe N, Filgueiras IS, Fonseca DLM, Hinterseher I, Catar RA, et al. Systematic review and meta-analysis of cell therapy for COVID-19: global clinical trial landscape, published safety/efficacy outcomes, cell product manufacturing and clinical delivery. Front Immunol. 2023;14:1200180. This systematic review and meta-analysis of cell therapy for COVID-19 provides the most comprehensive and up-to-date summary.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Moll G, Drzeniek N, Kamhieh-Milz J, Geissler S, Volk HD, Reinke P. MSC Therapies for COVID-19: importance of patient coagulopathy, thromboprophylaxis, cell product quality and mode of delivery for treatment safety and efficacy. Front Immunol. 2020;11:1091.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ringden O, Moll G, Gustafsson B, Sadeghi B. Mesenchymal stromal cells for enhancing hematopoietic engraftment and treatment of graft-versus-host disease, hemorrhages and acute respiratory distress syndrome. Front Immunol. 2022;13: 839844.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Huppert LA, Matthay MA, Ware LB. Pathogenesis of acute respiratory distress syndrome. Semin Respir Crit Care Med. 2019;40(1):31–9.

Article  PubMed  PubMed Central  Google Scholar 

•• Grasselli G, Tonetti T, Protti A, Langer T, Girardis M, Bellani G, et al. Pathophysiology of COVID-19-associated acute respiratory distress syndrome: a multicentre prospective observational study. Lancet Respir Med. 2020;8(12):1201–8. This prospective observational study on COVID-19 patients reports that there are clinical differences between classical ARDS and COVID-19-associated ARDS.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gattinoni L, Coppola S, Cressoni M, Busana M, Rossi S, Chiumello D. COVID-19 does not lead to a “typical” acute respiratory distress syndrome. Am J Respir Crit Care Med. 2020;201(10):1299–300.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hue S, Beldi-Ferchiou A, Bendib I, Surenaud M, Fourati S, Frapard T, et al. Uncontrolled innate and impaired adaptive immune responses in patients with COVID-19 acute respiratory distress syndrome. Am J Respir Crit Care Med. 2020;202(11):1509–19.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Matthay MA, Leligdowicz A, Liu KD. Biological mechanisms of COVID-19 acute respiratory distress syndrome. Am J Respir Crit Care Med. 2020;202(11):1489–91.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cruz FF, Weiss DJ, Rocco PR. Prospects and progress in cell therapy for acute respiratory distress syndrome. Expert Opin Biol Ther. 2016;16(11):1353–60.

Article  CAS  PubMed  Google Scholar 

Walter J, Ware LB, Matthay MA. Mesenchymal stem cells: mechanisms of potential therapeutic benefit in ARDS and sepsis. Lancet Respir Med. 2014;2(12):1016–26.

Article  CAS  PubMed  Google Scholar 

•• Tan Y, Wang Y, Souza-Moreira L, Wang C, Murray ABP, Salkhordeh M, et al. Mesenchymal stem cells induce dynamic immunomodulation of airway and systemic immune cells in vivo but do not improve survival for mice with H1N1 virus-induced acute lung injury. Front Bioeng Biotechnol. 2023;11:1203387. In this study, they demonstrate that MSC-based treatment has no survival benefit in influenza A virus-induced lung injury.

Article  PubMed  PubMed Central  Google Scholar 

Gotts JE, Abbott J, Matthay MA. Influenza causes prolonged disruption of the alveolar-capillary barrier in mice unresponsive to mesenchymal stem cell therapy. Am J Physiol Lung Cell Mol Physiol. 2014;307(5):L395-406.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Darwish I, Banner D, Mubareka S, Kim H, Besla R, Kelvin DJ, et al. Mesenchymal stromal (stem) cell therapy fails to improve outcomes in experimental severe influenza. PLoS ONE. 2013;8(8): e71761.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Qin A, Wang XJ, Fu J, Shen A, Huang X, Chen Z, et al. hMSCs treatment attenuates murine herpesvirus-68 (MHV-68) pneumonia through altering innate immune response via ROS/NLRP3 signaling pathway. Mol Biomed. 2023;4(1):27.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chan MC, Kuok DI, Leung CY, Hui KP, Valkenburg SA, Lau EH, et al. Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo. Proc Natl Acad Sci U S A. 2016;113(13):3621–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

•• Avanzini MA, Mura M, Percivalle E, Bastaroli F, Croce S, Valsecchi C, et al. Human mesenchymal stromal cells do not express ACE2 and TMPRSS2 and are not permissive to SARS-CoV-2 infection. Stem Cells Transl Med. 2021;10(4):636–42. In this study, they report that MSCs isolated from human tissues are not permissive to COVID-19 virus.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Simonson OE, Mougiakakos D, Heldring N, Bassi G, Johansson HJ, Dalen M, et al. In vivo effects of mesenchymal stromal cells in two patients with severe acute respiratory distress syndrome. Stem Cells Transl Med. 2016;5(6):845.

Article  PubMed  Google Scholar 

•• Bellingan G, Jacono F, Bannard-Smith J, Brealey D, Meyer N, Thickett D, et al. Safety and efficacy of multipotent adult progenitor cells in acute respiratory distress syndrome (MUST-ARDS): a multicentre, randomised, double-blind, placebo-controlled phase 1/2 trial. Intensive Care Med. 202

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