Mesenchymal Stem Cells: A New Piece in the Puzzle of COVID-19 Treatment

Abstract

COVID-19 is a disease characterized by a strong inflammatory response in severe cases, which fails to respond to corticosteroid therapy. In the context of the current COVID-19 outbreak and the critical information gaps regarding the disease, several different therapeutic strategies are under investigation, including the use of stem cells. In the present manuscript, we provide an analysis of the rationale underlying the application of stem cells to manage COVID-19, and also a comprehensive compendium of the 69 clinical trials underway worldwide aiming to investigate the application of stem cells to treat COVID-19. Even though data are still scarce, it is already possible to observe the protagonism of China in testing mesenchymal stem cells (MSCs) for COVID-19. Furthermore, it is possible to determine that current efforts focus on the use of multiple infusions of high numbers of stem cells and derived products, as well as to acknowledge the positive results obtained by independent groups who publicized the therapeutic benefits provided by such therapies in 51 COVID-19 patients. In such a rapid-paced field, up-to-date systematic studies and meta-analysis will aid the scientific community to separate hype from hope and offer an unbiased position to the society and governments.

Keywords: COVID-19; SARS-CoV-2; clinical trials; mesenchymal stem cells; stem cell-therapy.

Figure 1

Putative mechanisms of action of MSCs against lung inflammation caused by COVID-19. During SARS-CoV-2 infection, lung ACE-2 positive cells, such as epithelial and capillary endothelial cells are infected, leading to cell damage, inflammatory signaling, and the release of cytokines and chemokines. The inflammatory milieu promotes the activation of local macrophages, dendritic, and endothelial cells, which further secrete soluble factors and promote the migration of circulating monocytes, granulocytes, as well as lymphocytes. This leads to a feed-forward process, characterized by inflammation, tissue destruction, and organ dysfunction. MSCs and their secretome can be used to counteract inflammation through contact-dependent and also paracrine processes. MSCs, Mesenchymal Stem Cells; Tregs, Regulatory T-cells. Created with BioRender.com.

Figure 2

MSC-based strategies to treat COVID-19 under investigation in current clinical trials. Most clinical trials are based on the intravenous injection of allogeneic MSCs to treat COVID-19 patients. Other strategies include the isolation of MSC-derived exosomes, applied through inhalation, and also the temporary co-culture of autologous polymorphonuclear cells (PBMCs) collected from COVID-19 patients with allogeneic MSCs, followed by the injection of the so-called “educated” autologous PBMCs back to the COVID-19 patient. MSCs, Mesenchymal Stem Cells; PBMCs, Peripheral Blood Mononuclear Cells. Created with BioRender.com.