This review describes the origins, pathogenesis, and clinical features of COVID-19 and the potential uses of mesenchymal stem cells (MSCs) in therapeutic treatments for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients.

MSCs have previously been shown to have positive effects in the treatment of lung diseases, such as acute lung injury, idiopathic pulmonary fibrosis, acute respiratory distress syndrome, lung cancer, asthma, and chronic obstructive pulmonary disease. MSC mechanisms of action involve differentiation potentials, immune regulation, secretion of anti-inflammatory factors, migration and homing, anti-apoptotic properties, antiviral effects, and extracellular vesicles. Currently, 74 clinical trials are investigating the use of MSCs (predominately from the umbilical cord, bone marrow, and adipose tissue) to treat COVID-19. Although most of these trials are still in their early stages, the preliminary data are promising.

Mesenchymal stem cells (MSCs) have the capacity to self-renew and differentiate, and MSC-based therapies have received much attention in both basic medicine and clinical research. MSCs can be acquired from most human tissues, including but not limited to, bone marrow (BM), adipose tissue (AD), umbilical cord (UC), Wharton’s jelly (WJ), peripheral blood, menstrual blood, placenta, endometrium, amniotic membrane, amniotic fluid, fetal, dental pulp, urine, liver, lung, spleen, intestine, muscle, and synovium.

MSC-based therapies mainly rely on their self-renewal ability, pluripotent differentiation, low immunogenicity, anti-inflammatory function, and a homing ability to damaged tissues. Importantly, MSCs have a unique immuno-regulation mechanism for mediating innate and adaptive immune responses. Wilson et al. used allogeneic MSCs in patients with acute respiratory distress syndrome (ARDS) and found no adverse reactions, such as hypoxemia, arrhythmia, and ventricular tachycardia, and also showed good therapeutic effects. Another group reported that menstrual blood-derived MSC implantation significantly reduced the mortality of ARDS patients induced by the influenza A (H7N9) pandemic. Angiotensin-converting enzyme 2 (ACE2) has been verified as a receptor by which SARS-CoV-2 enters target cells. Interestingly, researchers have shown that MSCs do not express ACE2 and are resistant to SARS-CoV-2 infection. Therefore, MSC-based treatments may be promising for patients with COVID-19, especially those in which the disease is classified as severe or critical.

This review focuses on the potential mechanisms of MSCs and clinical studies using MSC transplantation for the treatment of COVID-19. The aim is to improve understanding of the current MSC-based treatments for COVID-19 and provide guidance for their further applications in clinical medicine.

The Authors conclusion is “MSC treatments for COVID-19 are currently lacking important long-term safety information and data from large-scale controlled trials, which is required to make conclusive judgments. With the continuous development of new technologies, we have come to understand that combined treatments can be more effective and advantageous, and that we should keep this in mind when considering treatments for COVID-19 in future. Thus, MSC-based treatments combined with other treatment methods could play a powerful role in developing effective strategies to combat COVID-19.”