Mesenchymal stromal cells to fight SARS-CoV-2: Taking advantage of a pleiotropic therapy

Abstract

The devastating global impact of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has prompted scientists to develop novel strategies to fight Coronavirus Disease of 2019 (COVID-19), including the examination of pre-existing treatments for other viral infections in COVID-19 patients. This review provides a reasoned discussion of the possible use of Mesenchymal Stromal Cells (MSC) or their products as a treatment in SARS-CoV-2-infected patients. The main benefits and concerns of using this cellular therapy, guided by preclinical and clinical data obtained from similar pathologies will be reviewed. MSC represent a highly immunomodulatory cell population and their use may be safe according to clinical studies developed in other pathologies. Notably, four clinical trials and four case reports that have already been performed in COVID-19 patients obtained promising results. The clinical application of MSC in COVID-19 is very preliminary and further investigational studies are required to determine the efficacy of the MSC therapy. Nevertheless, these preliminary studies were important to understand the therapeutic potential of MSC in COVID-19. Based on these encouraging results, the United States Food and Drug Administration (FDA) authorized the compassionate use of MSC, but only in patients with Acute Respiratory Distress Syndrome (ARDS) and a poor prognosis. In fact, patients with severe SARS-CoV-2 can present infection and tissue damage in different organs, such as lung, heart, liver, kidney, gut and brain, affecting their function. MSC may have pleiotropic activities in COVID-19, with the capacity to fight inflammation and repair lesions in several organs.

Keywords: COVID-19; Cytokine storm; Cytokines/chemokines; Mesenchymal stromal/stem cells; Pleiotropic therapy; SARS-CoV-2.

Fig. 1

Mesenchymal stromal cells (MSC) therapeutic potential to treat COVID-19. Upon entering the body, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is able to infect multiple organs (lungs, heart, liver, kidneys, gut and brain) by binding to Angiotensin-Converting Enzyme (ACE2) through its spike glycoproteins. ACE2 modulates the renin-angiotensin mechanism, thus the presence of the virus can lead to dysregulations in blood pressure. Moreover, SARS-CoV-2 can evoke an exacerbated inflammatory response which may lead to multi-organ injury. Besides, extensive damage in the parenchyma can increase the risk of opportunistic infections. MSC therapy is a promising treatment for COVID-19 as they exert potent anti-inflammatory and antimicrobial actions and promote tissue repair and regeneration through the secretion of soluble factors, extracellular vesicles and direct cell-to-cell contact. List of abbreviations: ACE2 - Angiotensin-Converting Enzyme 2; DCs - Dendritic Cells; GSCF - Granulocyte Colony-Stimulating Factor; FGF7 - Fibroblast Growth Factor 7; IFN-ϒ - Interferon ϒ; IL - Interleukin, MSC – Mesenchymal Stromal Cells, TNF - Tumor Necrosis Factor; Th - T helper; SARS-CoV-2 - Severe Acute Respiratory Syndrome Coronavirus 2.