Perinatal Cells: A Promising COVID-19 Therapy?

Abstract

The COVID-19 pandemic has become a priority in the health systems of all nations worldwide. In fact, there are currently no specific drugs or preventive treatments such as vaccines. The numerous therapies available today aim to counteract the symptoms caused by the viral infection that in some subjects can evolve causing acute respiratory distress syndromes (ARDS) with consequent admission to intensive care unit. The exacerbated response of the immune system, through cytokine storm, causes extensive damage to the lung tissue, with the formation of edema, fibrotic tissues and susceptibility to opportunistic infections. The inflammatory picture is also aggravated by disseminated intravascular coagulation which worsens the damage not only to the respiratory system, but also to other organs. In this context, perinatal cells represent a valid strategy thanks to their strong immunomodulatory potential, their safety profile, the ability to reduce fibrosis and stimulate reparative processes. Furthermore, perinatal cells exert antibacterial and antiviral actions. This review therefore provides an overview of the characteristics of perinatal cells with a particular focus on the beneficial effects that they could have in patients with COVID-19, and more specifically for their potential use in the treatment of ARDS and sepsis.

Keywords: PLacental eXpanded; coronavirus-induced disease 2019; mesenchymal stromal cells; perinatal; severe acute respiratory distress syndrome coronavirus-2.

Figure 1

Clinical trials using cell-based therapy for pulmonary disorders. (A) Clinical trials as reported on clinicaltrials.gov (as of July 1, 2020) with stromal cells for pulmonary conditions. Colors represent the different cells used in the studies. ARDS, acute respiratory distress syndrome; IPF, idiopathic pulmonary fibrosis; ILD, interstitial lung disease; COPD, chronic obstructive pulmonary disease. (B) Percentage of MSCs from different tissues used in COVID-19 clinical trials.

Figure 2

Etiopathology of the Sars-CoV2 viral infection and therapeutic effect of PDCs injection. (A) Sars-CoV2 is responsible for acute respiratory distress syndrome (ARDS) resulting in thousands of patients requiring intensive care unit (ICU) treatment. Importantly, the virus responsible of trigger an exacerbated immune response, resulting in a cytokine storm, and consequently to the damage of the epithelial airway, followed by lung edema, dysfunction of air exchange and the formation of interstitial fibrosis, thus creating an environment conducive to opportunistic bacterial infections or superinfection. Furthermore, COVID-19 is characterized also by the formation of vascular microthrombi that are often identified in areas of diffuse alveolar damage and are associated with diffuse endothelial damage. (B) PDCs treatment can directly affect the immune response through the release of immunomodulatory cytokines, such as IL-10, or anti-inflammatory molecules such as Prostaglandin (PG) E2, thus immunomodulating the exacerbated inflammatory response. Furthermore, MSCs can exert beneficial properties through the release of anti-microbial peptides such as LL-37. Moreover, PDCs can degrade or inhibit ARDS-induced fibrotic tissue by remodeling the extracellular matrix through the release of metalloprotease and TIMP, and modulation of the immune response can consequently reduce the formation of microthrombi affecting the alveolar capillaries. Created with Biorender.com.