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.
Highlights
Human Amniotic Fluid Stem Cells as Reservoir of Paracrine FactorsMesenchymal stromal cells (MSC) are progenitor cells that can be isolated from several tissues obtained from both adult and perinatal foetal tissue [1]
Human amniotic fluid-derived stem cells are immature MSC that can be obtained from extraembryonic annexes during gestation; human amniotic fluid (hAF)-MSC can be isolated as foetal stromal progenitor cells from leftover samples of routine prenatal screening (i.e., II trimester amniocentesis amniotic fluid sampling) or as perinatal progenitors at birth from clinical waste (i.e., III trimester term amniotic fluid obtained during scheduled Caesarean delivery) [2,3,4,5,6,7,8,9,10,11]. hAF-MSC have been described as multipotent cells that can be extensively and expanded and cryopreserved with stable karyotype due to their remarkable self-renewal profile, while not being tumorigenic and lacking ethical concerns [2,12,13,14]
Given the results reported by several independent lines of investigation, hAFS-extracellular vesicles (EVs) may represent an appealing source of therapeutics for several diseases
Summary
Mesenchymal stromal cells (MSC) are progenitor cells that can be isolated from several tissues obtained from both adult and perinatal foetal tissue (i.e., bone marrow, adipose tissue, cord blood, placenta, amniotic fluid, etc.) [1]. While some researchers have described the regenerative potential of RS- or SS-hAF-MSC obtained as the adherent stromal population retrieved from amniotic fluid [16,18,19,20], the enrichment of specific subpopulation, based on the specific expression of the stem cell factor c-KIT (CD117), has been reported to identify stem cells within the human amniotic fluid which may harbour the highest self-renewal potency, namely c-KIT+ human amniotic fluid-derived stem cells (hAFSC) [2,3] In these last 20 years, hAFSC have gained increasing attention as appealing source of immature stem cells that are multipotent, possess immunomodulatory properties and do not have the ethical and legal limitations of embryonic stem cells, being extensively investigated for tissue engineering applications as well as in transplantation strategies for the treatment of various degenerative and inflammatory diseases affecting major tissues/organ in either neonatal/paediatric patients and adult ones [12,21]. In this comprehensive review we will: (i) discuss the role of hAF-MSC/hAFSC-EVs (here collectively referred to as hAFS-EVs), as promising therapeutics for paediatric and adult disease; (ii) illustrate their characterization by comparing the current and most upto-date methods and technical challenges, and (iii) eventually consider the key role of hAF-EVs as candidate theranostic tools
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