Treatment of COVID-19 by Stage: Any Space Left for Mesenchymal Stem Cell Therapy?

Abstract

In many countries, COVID-19 now accounts for more deaths per year than car accidents and even the deadliest wars. Combating the viral pandemics requires a coordinated effort to develop therapeutic protocols adaptable to the disease severity. In this review article, we summarize a graded approach aiming to shield cells from SARS-CoV-2 entry and infection, inhibit excess inflammation and evasion of the immune response, and ultimately prevent systemic organ failure. Moreover, we focus on mesenchymal stem cell therapy, which has shown safety and efficacy as a treatment of inflammatory and immune diseases. The cell therapy approach is now repurposed in patients with severe COVID-19. Numerous trials of mesenchymal stem cell therapy are ongoing, especially in China and the USA. Leader companies in cell therapy have also started controlled trials utilizing their quality assessed cell products. Results are too premature to reach definitive conclusions.

Investigational Use of Mesenchymal Stem/Stromal Cells and Their Secretome as Add-On Therapy in Severe Respiratory Virus Infections: Challenges and Perspectives

“…Because of this unmet need, the therapeutic potential of mesenchymal stem/stromal cells (MSCs) and MSC-derived products is under evaluation in a huge number of clinical trials [36][37][38][39][40] on the basis of the results of preclinical studies that have demonstrated the ability of Table 1 Therapeutic management of hospitalized adult patients by disease severity. Source: published international guidelines [19,35] intravenously injected MSCs to transiently accumulate in the pulmonary circulation and to exert multiple beneficial effects, including the modulation of immunological responses, the prevention of bacterial superinfections, the promotion of the repair of damaged alveolocapillary barriers, and the alleviation of fibrosis in the injured lungs [40][41][42][43][44][45][46], mainly through paracrine signaling [42][43][44][45].…”

“…Source: published international guidelines [19,35] intravenously injected MSCs to transiently accumulate in the pulmonary circulation and to exert multiple beneficial effects, including the modulation of immunological responses, the prevention of bacterial superinfections, the promotion of the repair of damaged alveolocapillary barriers, and the alleviation of fibrosis in the injured lungs [40][41][42][43][44][45][46], mainly through paracrine signaling [42][43][44][45]. The MSCs under evaluation are a heterogeneous population of self-renewable multipotent cells that are most commonly harvested from the perinatal tissues (umbilical cord tissue, umbilical cord blood, or placenta), the menstrual blood, adult bone marrow or adult adipose tissue of one or more healthy unrelated donor(s) and are expanded in culture to large quantities for treating many patients [39,42,47,48]. The investigational therapy is either the allogeneic population of MSCs expanded in culture or its secretome, which is composed of soluble factors and extracellular vesicles such as exosomes and microvesicles [38,45].…”

Commentary: Mending a broken heart: The ongoing quest for mesenchymal stem cell therapy for ischemic cardiomyopathy

“…Indeed, the immunomodulatory action of MSCs has prompted their testing as a therapy for coronavirus disease 2019. 9 Induced pluripotent stem cells represent promising candidates, overcoming limitations of embryonic stem cell-derived cardiomyocytes, 10 showing regenerative capabilities in nonhuman primates. 11 However, being newly differentiated, plastic cells, they demand further studies before clinical translation to exclude risk of tumorigenesis.…”