Stalling SARS-CoV2 infection with stem cells: can regenerating perinatal tissue mesenchymal stem cells offer a multi-tiered therapeutic approach to COVID-19?

Abstract

The emergence of COVID-19 has created a major health crisis across the globe. Invasion of SARS-CoV-2 into the lungs causes acute respiratory distress syndrome (ARDS) that result in the damage of lung alveolar epithelial cells. Currently, there is no standard treatment available to treat the disease and the resultant lung scarring is irreversible even after recovery. This has prompted researchers across the globe to focus on developing new therapeutics and vaccines for the treatment and prevention of COVID-19. Mesenchymal stem cells (MSCs) have emerged as an efficient drug screening platform and MSC-derived organoids has found applications in disease modeling and drug discovery. Perinatal tissue derived MSC based cell therapies have been explored in the treatment of various disease conditions including ARDS because of their enhanced regenerative and immunomodulatory properties. The multi-utility properties of MSCs have been described in this review wherein we discuss the potential use of MSC-derived lung organoids in screening of novel therapeutic compounds for COVID-19 and also in disease modeling to better understand the pathogenesis of the disease. This article also summarizes the rationale behind the development of MSC-based cell- and cell-free therapies and vaccines for COVID-19 with a focus on the current progress in this area. With the pandemic raging, an important necessity is to develop novel treatment strategies which will not only alleviate the disease symptoms but also avoid any off-target effects which could further increase post infection sequelae. Naturally occurring mesenchymal stem cells could be the magic bullet which fulfil these criteria.

Keywords: COVID-19; Cell therapy; Exosomes; Mesenchymal stem cells; SARS-CoV2.

Fig. 1

Role of mesenchymal stem cells (MSCs) in drug screening. Lung organoids expressing viral target proteins such as ACE2 generated by the differentiation of MSCs isolated from perinatal tissues are excellent model systems in novel drug screening and to study host-virus interaction in the pathogenesis of Covid-19.

Fig. 2

Diagrammatic representation of cell free therapy. Exosomes isolated from mesenchymal stem cells (MSCs) can be delivered via intranasal route that will act against SARS-CoV-2 through immunomodulation and inhibiting viral replication.