HOW MESENCHYMAL STEM CELLS WORK AGAINST COVID-19?

A person who lives in twenty-first century will not forget word “COVID-19”.Corona virus (COVID-19) has grown very rapidly in the whole world from December 2019. COVID-19 named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in February 2020 by International Committee on Taxonomy of Viruses (ICTV). A patient of coronavirus disease was first detected in Wuhan, China, in December 2019 and then it has grown to be a global disease (Zhao, R. C., 2020).

Seeking treatments against COVID-19:
Many researchers or scientists who are belongs to biomedical fields are seeking treatments, medication or solution against COVID 19. For the curing of covid-19 multiple medicines are investigated including anti-inflammatory, anti-viral and anti-malarial agents. However, no specified treatment for COVID-19 has been discovered yet. Perhaps, preventing infection of the acute respiratory distress syndrome (ARDS) form of coronavirus 19 as the very dangerous stage of this disease could be very helpful for treatment also for reduce death rate. In this article, we specifically focus on the Mesenchymal stem cells that work against covid-19 (Golchin, A., et al., 2020).

What are Mesenchymal Stem Cells (MSCs)?
MSCs are the multipotent stem cells and these cells are present in bone marrow. Mesenchymal stem cells are very essential for repairing and making skeletal tissues, for example cartilage, fat and bone. Mesenchymal stem cells are considered to have comprehensive bioactivities, comprising repair, improved clearance of alveolar fluid, immunomodulation and pulmonary vascular endothelial permeability regulation (Xiao, K., et al., 2020).

Clinical trials of MSCs for the treatment of COVID-19:
Several clinical trials are being carried out on mesenchymal stem cells as a novel treatment for patients who are suffered in COVID-19 disease. There is none any approved impressive therapy for COVID-19 patients, but mesenchymal stem cells therapy has shown first effective promise in curing of acute respiratory distress syndrome pneumonia and inflammation (Moll. G.,et al., 2020).

Role of Mesenchymal Stem Cells in COVID-19 patients:
Cell-based therapies specifically stem cell therapy has grown as auspicious therapeutic field, offers various opportunities for treatment of incurable diseases. Among these, mesenchymal stem cells have attracted more consideration because of source potential, low aggressive procedure, and none of the ethical issues. The immune system of COVID-19 patient’s produces inflammatory factors are in abundance, producing a cytokine storm including, in an abundance of cytokines and immune cells. Mesenchymal stem cell therapy can prevent release of cytokines storm through the immune system also encourages endogenous reparation via reparative characteristics of the stem cells. After the intravenous (IV) infusion, small amount of MSCs trap in the lungs. Mesenchymal stem cells could recuperate the microenvironment of pulmonary, interrupt pulmonic fibrosis, alveolar epithelial cells protect and COVID-19 pneumonia (Golchin, A., 2020).

Mechanisms of action of Mesenchymal Stem Cells in ARDS:
Mesenchymal stem cells (MSCs) act by soluble factors and extracellular vesicles secretion and transfer of mitochondria. It promotes endothelial and epithelial repair, utilizes anti-inflammatory, clearance of alveolar fluid and bacteria. MSCs discharge peptide LL37 and neutrophil intravasations inhibit and formation of Neutrophil extracellular traps. In M1 type macrophages, phagocytosis increase and bacterial clearance promote by MSCs. Mesenchymal stem cells activate T cells via inhibiting propagation and activation. Mesenchymal stem cells increase the macrophages differentiation to M2 phenotype; anti-inflammatory cytokines are produce and proinflammatory factors (TNF-α, IL-6, and IL-1β) are inhibited (figure 1). These are very helpful in tissue reparation as well as prevent the discharge of cytokine storms.At the same time, Na+-K+-ATPase is upregulated in lung Alveolar Type-II cells and prevents fibrosis. MSCs promote the alveolar fluid clearance via increasing fibroblast growth factor 7 (FGF7) and angiopoietin-1 (Ang-1) level. In addition to decreasing the cytokine storms production by the immune system, Mesenchymal stem cell therapy also helps in endogenous reparation, lung microenvironments restore, alveolar epithelial cells protection and COVID-19 pneumonia cure. Mesenchymal stem cells promote the type II alveolar epithelial cells regeneration by production of keratinocyte growth factor (KGF), hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF). Mesenchymal stem cells also prevent the endothelial cells apoptosis and also contribute in reparation of alveolar epithelial barrier in acute respiratory distress syndrome (ARDS) related injury to improve the repairing of damaged lung tissues in patients of COVID-19 with acute respiratory distress syndrome (Xiao,K., et al., 2020).

REFERENCES:
 
1. Robert Chunhua Zhao. (2020). Stem Cell–Based Therapy for Coronavirus Disease 2019, Stem Cells and Development.

2. Guido Moll, Norman Drzeniek, Julian Kamhieh-Milz, Sven Geissler, Hans-Dieter Volk, Petra Reinke. (2020). Mesenchymal Stromal Cell Therapies for COVID-19: Importance of Patient Coagulopathy, Thromboprophylaxis, and Cell Product Quality for Treatment Safety and Efficacy, Front. Immunol.

3. Ali Golchin, Ehsan Seyedjafari, Abdolreza Ardeshirylajimi. (2020). Mesenchymal Stem Cell Therapy for COVID-19: Present or Future, Stem Cell Rev and Rep.

4. Xiao, K., Hou, F., Huang, X., Li, B., Qian, Z. R., & Xie, L. (2020). Mesenchymal stem cells: current clinical progress in ARDS and COVID-19. Stem Cell Research & Therapy.

By: Sadia Israr