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

Mesenchymal stem cells (MSCs), as adult multipotent cells, possess considerable regenerative and anti-neoplastic effects, from inducing apoptosis in the cancer cells to reducing multidrug resistance that bring them up as an appropriate alternative for cancer treatment. These cells can alter the behavior of cancer cells, the condition of the tumor microenvironment, and the activity of immune cells that result in tumor regression. It has been observed that during inflammatory conditions, a well-known feature of the tumor microenvironment, the MSCs produce and release some molecules called “antimicrobial peptides (AMPs)” with demonstrated anti-neoplastic effects. These peptides have remarkable targeted anticancer effects by attaching to the negatively charged membrane of neoplastic cells, disrupting the membrane, and interfering with intracellular pathways. Therefore, AMPs could be considered as a part of the wide-ranging anti-neoplastic effects of MSCs. This review focuses on the possible anti-neoplastic effects of MSCs-derived AMPs and their mechanisms. It also discusses preconditioning approaches and using exosomes to enhance AMP production and delivery from MSCs to cancer cells. Besides, the clinical administration of MSCs-derived AMPs, along with their challenges in clinical practice, were debated.