Human placenta-derived amniotic epithelial cells as a new therapeutic hope for COVID-19-associated acute respiratory distress syndrome (ARDS) and systemic inflammation

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has become in the spotlight regarding the serious early and late complications, including acute respiratory distress syndrome (ARDS), systemic inflammation, multi-organ failure and death. Although many preventive and therapeutic approaches have been suggested for ameliorating complications of COVID-19, emerging new resistant viral variants has called the efficacy of current therapeutic approaches into question. Besides, recent reports on the late and chronic complications of COVID-19, including organ fibrosis, emphasize a need for a multi-aspect therapeutic method that could control various COVID-19 consequences. Human amniotic epithelial cells (hAECs), a group of placenta-derived amniotic membrane resident stem cells, possess considerable therapeutic features that bring them up as a proposed therapeutic option for COVID-19. These cells display immunomodulatory effects in different organs that could reduce the adverse consequences of immune system hyper-reaction against SARS-CoV-2. Besides, hAECs would participate in alveolar fluid clearance, renin–angiotensin–aldosterone system regulation, and regeneration of damaged organs. hAECs could also prevent thrombotic events, which is a serious complication of COVID-19. This review focuses on the proposed early and late therapeutic mechanisms of hAECs and their exosomes to the injured organs. It also discusses the possible application of preconditioned and genetically modified hAECs as well as their promising role as a drug delivery system in COVID-19. Moreover, the recent advances in the pre-clinical and clinical application of hAECs and their exosomes as an optimistic therapeutic hope in COVID-19 have been reviewed. Graphical abstract

Unraveling the Emerging Niche Role of Hepatic Stellate Cell-derived Exosomes in Liver Diseases

“…Exosomes have a diameter of 40-160 nm and they are released by all types of cells. 7,8 Exosomes can be found in almost all body fluids, such as plasma, 9 urine, 10 cerebrospinal fluid, 11 saliva, 12 breast milk, 13 joint fluid, 14 amniotic fluid, 15 and semen. 16 Of note, some special proteins are found on the surface of exosome vesicles, such as HSP70, CD9, CD63, CD62, and CD81.…”

Comparative Analysis of Co-Cultured Amniotic Cell-Conditioned Media with Cell-Free Amniotic Fluid Reveals Differential Effects on Epithelial–Mesenchymal Transition and Myofibroblast Activation

“…These bodies of literature suggest that AECs and AFCs have the potential to effectively treat a variety of conditions, ranging from cutaneous wounds to orthopedic conditions, to liver or lung disorders, and neurological conditions. While some efficacy has been shown in certain clinical contexts [ 59 , 60 , 61 ], it is clear that these treatments are safe when properly administered [ 62 , 63 ]. Furthermore, the therapeutic effects appear to be mediated not necessarily by the cells directly, but by their secreted trophic factors [ 64 , 65 , 66 , 67 , 68 ].…”

The favorable impacts of silibinin polyphenols as adjunctive therapy in reducing the complications of COVID-19: A review of research evidence and underlying mechanisms

“…1 ) [11] , [12] . It is assumed that the cytokine storm and hypercoagulation of the hyper-inflammation phase contribute to disease severity and mortality [13] . In this regard, critically ill patients with COVID-19 have displayed higher levels of neutrophils, pro-inflammatory cytokines, and ROS [14] .…”