Coronaviruses are pathogenic microorganisms that pose a serious threat to human and animal health and are known to cause colds and more serious diseases, such as Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS). To date, however, there is no specific treatment for SARS-CoV, MERS-CoV, SARS-CoV-2 and other HCoV infections. Fortunately, the COVID-19 vaccine has been marketed with the joint efforts of various countries. Upon vaccination, the body can be stimulated to produce corresponding protective antibodies, thereby mitigating the risk of infection with SARS-CoV-2. Nevertheless, SARS-CoV-2 virus remains cryptic up to now as its many features including transmission, infection, and treatment are still waiting for unraveling. The virus has undergone various mutations that may influence the effectiveness of antibodies.
Stem cells, especially mesenchymal stem cells (MSCs), have powerful immune regulation and tissue damage repair functions. In recent years, MSCs and lung stem/progenitor cells (LSCs) have been widely used in the treatment of viral infections and various diseases, including acute lung injury (ALI).
Current studies have shown that MSCs can effectively reduce the severe inflammatory response in patients caused by SARS-CoV-2, reduce lung injury, improve lung function, protect and repair the lung, and play a positive role in alleviating pulmonary fibrosis in COVID-19 patients.
Symptoms of COVID-19 vary widely among individuals, ranging from asymptomatic infection to critical illness. A medical observation of 47 patients in the early stage of the epidemic found that fever, fatigue and dry cough were the main manifestations of COVID-19, and a few patients had expectoration and diarrhea. Most severe cases develop dyspnea or hypoxemia within a week and even rapidly developed ARDS, septic shock, metabolic acidosis and coagulation dysfunction in severe cases. COVID-19 symptoms occur after an incubation period of approximately 5.2 days of infection, and the time from symptom onset to death ranges from 6 to 41 days.
Cell therapy is a significant treatment that has been applied in a variety of diseases, including lung, cardiovascular, liver, kidney and other diseases. Stem cells are primitive cells with self-renewal ability and multidirectional differentiation potential and can differentiate into a variety of functional cells or tissues. Stem cell therapy involves cultivating new, normal, younger cells, tissues and even micro organs through isolation, culture, and directed differentiation of the stem cells in vitro and then transplanting them to specific parts of the body instead of the cells that are damaged or have died, thereby restoring body functions. Stem cell therapy is available not only for severe COVID-19 patients but also to those who have recovered from severe COVID-19 complications to repair damaged lungs, making it an ideal treatment.
Human umbilical cord derived MSCs (hUC-MSCs)
The umbilical cord (especially Wharton’s jelly) is different from the bone marrow and contains a high concentration of MSCs. It is one of the most abundant sources of MSC. MSCs derived from the human umbilical cord (hUC-MSCs) can be extracted noninvasively, and the cells proliferate rapidly, making them the most suitable stem cells for the treatment of COVID-19. In patients treated with hUC-MSCs, the PaO2/FiO2 ratio improved, and the IL-6 level decreased. Chest CTs showed that the lung lesions of patients with hUC-MSC infusion were well controlled within 6 days and disappeared completely within 2 weeks.
It was reported the efficacy and safety of the infusion of hUC-MSCs for severe COVID-19, with an intravenous infusion of UC-MSCs performed in 12 patients with severe COVID-19. The results showed that compared with the control group, the hUC-MSC infusion could reduce the levels of inflammatory CRP and IL-6, accelerate the recovery of the lymphocyte count and shorten the absorption period of lung inflammation. In addition, the hUC-MSC infusion improved the clinical symptoms of weakness and fatigue, tachypnea, and hypoxia. The 28-day mortality of the treatment group was 0, while that of the control group was 10.34%.
In addition to regulating immunity, MSCs also have promising advantages in the treatment of lung injury and repair caused by viral infections. MSCs have the potential function of multipotent differentiation and can produce a variety of cytokines and growth factors, which can treat or repair virus-induced lung tissue damage by affecting other cell signaling pathways.
After an intravenous injection, some of the MSCs homing in the lungs can differentiate into alveolar epithelial cells and pulmonary vascular endothelial cells, which can increase the secretion of alveolar surface active substances and promote vascular regeneration, thus promoting injury repair. In addition, MSCs can also promote the repair of other damaged tissues in patients with COVID-19. Studies have shown that MSCs activate a variety of repair mechanisms by secreting cytokines, including anti-inflammatory and anti-apoptotic effect factors, and promote angiogenesis to promote the repair of the kidney and intestine.