The Coronavirus Pandemic: A Pitfall or a Fast Track for Validating Cell Therapy Products?

The global COVID-19 pandemic has prompted urgent need for potential therapies for severe respiratory consequences resulting from coronavirus infection. New therapeutic agents that will attenuate ongoing inflammation and at the same time promote regeneration of injured lung epithelial cells are urgently needed. Cell-based therapies, primarily involving mesenchymal stromal cells (MSCs) and their derivatives, are currently investigated worldwide for SARS-CoV-2-induced lung diseases. A significant number of academic centers and companies globally have already initiated such trials. However, at a time of unprecedented need, it is also foreseen that families and caregivers will seek all available options, including access to cell-based and other investigational products, even before proven safety and efficacy as well as regulatory approval. This should not be an excuse for opportunists to sell or advertise unproven therapies of any kind. "Compassionate use" should be conducted in the context of a clinical investigation framed by strict ethical and regulatory permissions, with the goal of obtaining mechanistic information wherever possible.

Cell-based therapies for coronavirus disease 2019: proper clinical investigations are essential.

The serious consequences of the global coronavirus disease 2019 (COVID-19) pandemic have prompted a rapid global response to develop effective therapies that can lessen disease severity in infected patients. Cell-based approaches, primarily using mesenchymal stromal cells (MSCs), have demonstrated a strong safety profile and possible efficacy in patients with acute respiratory distress syndrome (ARDS), but whether these therapies are effective for treating respiratory virus-induced ARDS is unknown. According to the World Health Organization International Clinical Trials Registry Platform and the National Institutes of Health ClinicalTrials.gov databases, 27 clinical investigations of MSC-based cell therapy approaches have begun in China since the onset of the COVID-19 outbreak, with a growing number of academic and industry trials elsewhere as well. Several recent published reports have suggested potential efficacy; however, the available data presented are either anecdotal or from incomplete, poorly controlled investigations. Therefore, although there may be a potential role for MSCs and other cell-based therapies in treatment of COVID-19, these need to be investigated in a rationally designed, controlled approach if safety and efficacy are to be demonstrated accurately. The authors urge that the field proceed by finding a balance between swift experimentation and communication of results and scientifically coherent generation and analysis of clinical data.

Current status of cell-based therapies for respiratory virus infections: applicability to COVID-19.

The severe respiratory consequences of the coronavirus disease 2019 (COVID-19) pandemic have prompted urgent need for novel therapies. Cell-based approaches, primarily using mesenchymal stem (stromal) cells (MSCs), have demonstrated safety and possible efficacy in patients with acute respiratory distress syndrome (ARDS), although they are not yet well studied in respiratory virus-induced ARDS. Limited pre-clinical data suggest that systemic MSC administration can significantly reduce respiratory virus (influenza strains H5N1 and H9N2)-induced lung injury; however, there are no available data in models of coronavirus respiratory infection.There is a rapidly increasing number of clinical investigations of cell-based therapy approaches for COVID-19. These utilise a range of different cell sources, doses, dosing strategies and targeted patient populations. To provide a rational strategy to maximise potential therapeutic use, it is critically important to understand the relevant pre-clinical studies and postulated mechanisms of MSC actions in respiratory virus-induced lung injuries. This review presents these, along with consideration of current clinical investigations.