Current status of mesenchymal stem cell therapy for immune/inflammatory lung disorders: Gleaning insights for possible use in COVID-19

Abstract

The broad immunomodulatory properties of human mesenchymal stem cells (MSCs) have allowed for wide application in regenerative medicine as well as immune/ inflammatory diseases, including unmatched allogeneic use. The novel coronavirus disease COVID-19 has unleashed a pandemic in record time accompanied by an alarming mortality rate mainly due to pulmonary injury and acute respiratory distress syndrome. Because there are no effective preventive or curative therapies currently, MSC therapy (MSCT) has emerged as a possible candidate despite the lack of preclinical data of MSCs for COVID-19. Interestingly, MSCT preclinical data specifically on immune/inflammatory disorders of the lungs were among the earliest to be reported in 2003, with the first clinical use of MSCT for graft-vs-host disease reported in 2004. Since these first reports, preclinical data showing beneficial effects of MSC immunomodulation have accumulated substantially, and as a consequence, over a third of MSCT clinical trials now target immune/inflammatory diseases. There is much preclinical evidence for MSCT in noninfectious-including chronic obstructive pulmonary disease, asthma, and idiopathic pulmonary fibrosis-as well as infectious bacterial immune/inflammatory lung disorders, with data generally demonstrating therapeutic effects; however, for infectious viral pulmonary conditions, the preclinical evidence is more scarce with some inconsistent outcomes. In this article, we review the mechanistic evidence for clinical use of MSCs in pulmonary immune/inflammatory disorders, and survey the ongoing clinical trials-including for COVID-19-of MSCT for these diseases, with some perspectives and comment on MSCT for COVID-19.

Mesenchymal Stromal Cells in Viral Infections: Implications for COVID-19

“…Nevertheless, any consideration of MSC-based therapy for COVID-19 should be focused on very severe/critical cases characterized by decontrolled immune response, and critical ARDS and systemic organ involvement [5,123,127]. We strongly argue that MSCs should not be infused during the early period of viral infection, where inflammation is very important and beneficial to contain viral infection.…”

“…Nowadays, the COVID-19 pandemic represents a public health emergency and has prompted an urgent need for novel or alternative therapies [5,103,105,[123][124][125][126][127]. Almost every patient with COVID-19 presents with lung involvement, whereas severe complications, such as ARDS, are only observed in a subgroup of severe patients.…”

“…In addition, intravenously infused MSCs become trapped in the lung. In the case of COVID-19, this fact may be beneficial as the lung is the primary organ affected by SARS-CoV-2 [5,103,105,[123][124][125][126][127].…”

“…Moreover, several challenges still have to be addressed, especially MSC dosing and timing of administration, since an exacerbated immunosuppression may have the reverse effect [5,103,105,[123][124][125][126][127]. The MSC-based clinical trials should be carefully designed (randomized; placebocontrolled; large patient cohorts) to ensure that the results will be effective, accurate, trustworthy and significant.…”

Chronic obstructive lung disease and COVID-19: topical issues

“…На данный момент инициировано 31 исследование по применению мезенхимальных стволовых клеток у больных с новой коронавирусной инфекцией COVID-19. Потенциальной клинической «мишенью» для данного метода терапии будут являться тяжелые случаи COVID-19 с развитием ОРДС и выраженным «цитокиновым штормом» [53].…”