Therapeutic Applications of Stem Cells and Extracellular Vesicles in Emergency Care: Futuristic Perspectives

Abstract

Regenerative medicine (RM) is an interdisciplinary field that aims to repair, replace or regenerate damaged or missing tissue or organs to function as close as possible to its physiological architecture and functions. Stem cells, which are undifferentiated cells retaining self-renewal potential, excessive proliferation and differentiation capacity into offspring or daughter cells that form different lineage cells of an organism, are considered as an important part of the RM approaches. They have been widely investigated in preclinical and clinical studies for therapeutic purposes. Extracellular vesicles (EVs) are the vital mediators that regulate the therapeutic effects of stem cells. Besides, they carry various types of cargo between cells which make them a significant contributor of intercellular communication. Given their role in physiological and pathological conditions in living cells, EVs are considered as a new therapeutic alternative solution for a variety of diseases in which there is a high unmet clinical need. This review aims to summarize and identify therapeutic potential of stem cells and EVs in diseases requiring acute emergency care such as trauma, heart diseases, stroke, acute respiratory distress syndrome and burn injury. Diseases that affect militaries or societies including acute radiation syndrome, sepsis and viral pandemics such as novel coronavirus disease 2019 are also discussed. Additionally, featuring and problematic issues that hamper clinical translation of stem cells and EVs are debated in a comparative manner with a futuristic perspective.

Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying miRNA as a Potential Multi Target Therapy to COVID-19: an In Silico Analysis

“…Apoptotic bodies, 50-2000 nm, are vesicles released from the cell surface through outward budding of apoptotic cell membrane [41]. The MSCs-derived EVs can carry inside their lipidic bilayer, proteins, messenger RNAs (mRNAs), small and long non-coding RNAs (ncRNAs), DNA, lipids, and carbohydrates from parental cells which could shape the behavior of target cells contributing to the angiogenic, immunomodulatory and regenerative effect [42][43][44]. Thereby, the MSC-derived EVs present themselves as potentially cell-free agents on account of their similar characteristics with the parental cells.…”

“…Thereby, the MSC-derived EVs present themselves as potentially cell-free agents on account of their similar characteristics with the parental cells. The benefits of EVs are the minimal risk of getting trapped in the lungs, production as "off-the-shelf" products in large quantities, minimal risk of tumor formation, non-immunogenic profile, ability to cross natural barriers and deliver bioactive compounds and others [44]. Studies using EVs in ARDS are incipient, but there are studies showing MSC-derived EVs present similar effects when compared to administration of MSCs [45,46].…”

Spheroids and organoids as humanized 3D scaffold‐free engineered tissues for SARS‐CoV‐2 viral infection and drug screening

“…Another recent approach to combat SARS‐CoV‐2 is the therapeutic use of extracellular vesicles derived from adult stem cells, due to their effect on the modulation of anti‐inflammatory and antiapoptotic pathways. The extracellular vesicles were already tested in acute respiratory distress syndrome and promise a novel treatment for the patients with COVID‐19 15 . Furthermore, the efficacy of extracellular vesicles could be tested using 3D cell culture models.…”

“…The extracellular vesicles were already tested in acute respiratory distress syndrome and promise a novel treatment for the patients with COVID-19. 15 Furthermore, the efficacy of extracellular vesicles could be tested using 3D cell culture models.…”

Microfluidic Tools for Enhanced Characterization of Therapeutic Stem Cells and Prediction of Their Potential Antimicrobial Secretome

“…The EVs released from MSCs retain antimicrobial characteristics [13] and are considered to be safer than parent cell administration [17]. The EVs as cell-free agents and/or drug carriers may have therapeutic functions in sepsis [18] and may evolve into superior drug delivery tools. The presence of AMPs in the cargo of EVs may represent the next cell-free therapy option against resistant bacterial infections.…”