Small Extracellular Vesicles from Human Amniotic Fluid Samples as Promising Theranostics

Abstract

Since the first evidence that stem cells can provide pro-resolving effects via paracrine secretion of soluble factors, growing interest has been addressed to define the most ideal cell source for clinical translation. Leftover or clinical waste samples of human amniotic fluid obtained following prenatal screening, clinical intervention, or during scheduled caesarean section (C-section) delivery at term have been recently considered an appealing source of mesenchymal progenitors with peculiar regenerative capacity. Human amniotic fluid stem cells (hAFSC) have been demonstrated to support tissue recovery in several preclinical models of disease by exerting paracrine proliferative, anti-inflammatory and regenerative influence. Small extracellular vesicles (EVs) concentrated from the hAFSC secretome (the total soluble trophic factors secreted in the cell-conditioned medium, hAFSC-CM) recapitulate most of the beneficial cell effects. Independent studies in preclinical models of either adult disorders or severe diseases in newborns have suggested a regenerative role of hAFSC-EVs. EVs can be eventually concentrated from amniotic fluid (hAF) to offer useful prenatal information, as recently suggested. In this review, we focus on the most significant aspects of EVs obtained from either hAFSC and hAF and consider the current challenges for their clinical translation, including isolation, characterization and quantification methods.

The Glyoxalase System Is a Novel Cargo of Amniotic Fluid Stem-Cell-Derived Extracellular Vesicles

“…Or can the system be a novel mediator in intercellular communication from donor to recipient cells? Remarkably, EVs have been shown to affect several biological processes, such as cell migration, angiogenesis, inflammation, tissue repair and regeneration through their paracrine cargo [ 46 ]. Hence, the glyoxalase system could be a novel previously undiscovered actor in all these biological responses.…”

“…Hence, the glyoxalase system could be a novel previously undiscovered actor in all these biological responses. In addition, since EVs derived from stem cells may be envisioned as attractive medicinal therapeutic products for future cell-free paracrine treatment, also in consideration of their presumed low immunogenicity [ 46 ], the glyoxalase system could also play a role in this fascinating applicative ambit. Interestingly, since also autophagosomes can be a source of EVs, through the “secretory autophagy” pathway [ 47 ], and autophagy, as well as glyoxalases, participate to maintain cellular homeostasis and longevity [ 48 , 49 ], it is also fascinating to hypothesize that glyoxalase-containing EVs might be somehow involved in aging control.…”

Investigating the Paracrine Role of Perinatal Derivatives: Human Amniotic Fluid Stem Cell-Extracellular Vesicles Show Promising Transient Potential for Cardiomyocyte Renewal

“…Notably, hAFSC have been shown to sustain tissue recovery by exerting proliferative, anti-inflammatory, and trophic influence. The relevant paracrine effects of the fetal hAFSC secretome (namely the total amount of soluble factors that cells can secrete in their culture medium, i.e., the cell-conditioned medium, hAFSC-CM), including their released membrane-derived extracellular vesicles (hAFSC-EVs) have been assessed in preclinical models of injury, as comprehensively reviewed in Costa et al (2022 ). Indeed, the emphasis on mesenchymal stromal cell–based therapy has moved toward the profiling of their secreted EVs, since they have been generally described to convey enriched trophic factors and regulating RNAs orchestrating intercellular communication and have a functional impact on target cells.…”

The Role of Exosomes in Health and Disease

“…At the time, it was surprising to observe how maturing blood reticulocytes secreted transferrin receptors within hitherto unexpected tiny membranous vesicles, later named exosomes by Dr. Rose M Johnstone. Today, we know that nanovesicles release is an extraordinary mode of communication of all cells in health and disease throughout life [ 3 , 4 , 5 ], even in dying cells [ 6 ]. However, not all extracellular vesicles (EVs) are the same.…”