Mesenchymal Stem Cell Infusion Shows Promise for Combating Coronavirus-Induced Pneumonia
DY Patil School of Biotechnology and Bioinformatics
A new study published in the journal Aging and Disease reported that the intravenous administration of clinical-grade human mesenchymal stem cells into patients with COVID-19 resulted in improved functional outcomes. COVID-19 is a severe acute respiratory syndrome. Mild symptoms include fever, cough, and shortness of breath, and severe infection can lead to death.
HCoV-19 virus recognizes the angiotensin I converting enzyme 2 receptor (ACE2) by its spike protein. ACE2-positive cells are infected by the HCoV-19. It was revealed by a research team from Germany that the cellular serine protease TMPRSS2 for HCoV-19 Spike protein priming is also essential for the host cell entry and spread. The ACE2 receptor is widely distributed on the alveolar type II cells (AT2) and capillary endothelium, and the AT2 cells highly express TMPRSS2. Cells such as T and B lymphocytes, macrophages, bone marrow, lymph nodes tested negative for ACE2. Acute infection results in the cytokine storm, which causes edema, air exchange dysfunction, acute respiratory distress, which may lead to death in severe cases.ACE2 expression is also widely observed in other tissues such as the heart, liver, kidney, and digestive organs. Treating COVID_19 patients, especially those afflicted with severe pneumonia is challenging as there is no specific drug available.
Mesenchymal stem cells have been used in cell-based therapy. MSCs have the differential ability and immunomodulatory effects. The safety and efficiency of MSC have been shown in many clinical trials. A pilot study was conducted on seven patients with COVID-19 pneumonia in China where intravenous MSC transplant was performed. The patients were tested positive for SARS-CoV-2, with one displaying critically severe type, 4 exhibiting severe types, and the other 2showing common types of the syndrome. The patients were observed for 14 days after the introduction of the infused MSCs. The total number of transplant cells calculated was 1×106 cell per kilogram of weight. The early symptoms before the drug administration were high fever, weakness, shortness of breath, low oxygen saturation. After 2-4 days of transplantation, all the symptoms disappeared in all patients. The anti-inflammatory property of MSCs resulted in the improvement after the MSC infusion. The beneficial outcomes included an increased number of peripheral lymphocytes and a decline in the C-reactive protein and the disappearance of overactivated cytokine-secreting immune cells by 3-6 days in the circulating blood. A group of CD 14ᐩ CD11cᐩ CD11 bmid regulatory dendritic cell populations increased after MSC treatment The patients receiving MSC infusion displayed a decreased level of tumor necrosis factor-alpha, a major pro-inflammatory cytokine. As it has been proven by 10 × RNA- sequencing that infused MSCs were tested negative for ACE2 and TMPRSS2, MSCs are free from COVID-19 infection.
MSC infusion reduces overactivation of the immune system and supports repair by modulating the lung microenvironment. Intravenous infusion of MSC results in their accumulation in lungs, here they secrete multiple paracrine factors, these factors play a role in protecting or rejuvenating alveolar epithelial cells, counteracting fibrosis, and treating pneumonia. As the elderly population is more susceptible to SARS-CoV-2 induced pneumonia, this method can be very beneficial to them. Intravenous MSC infusion has shown no side effects, hence can be a good therapy against COVID-29 induced pneumonia. Therefore, in conclusion, it has been proven by clinical tests that intravenous infusion of MSC is a safe and efficient method for treating patients with COVID-19 pneumonia, including elderly patients with severe pneumonia. However, additional studies and trials on patients on a larger scale to validate the therapy are still needed.