The Bottlenecks in Translating Placenta-Derived Amniotic Epithelial and Mesenchymal Stromal Cells Into the Clinic: Current Discrepancies in Marker Reports

Abstract

Placenta-derived amniotic cells have prominent features for application in regenerative medicine. However, there are still discrepancies in the characterization of human amniotic epithelial and mesenchymal stromal cells. It seems crucial that the characterization of human amniotic membrane cells be investigated to determine whether there are currently discrepancies in their characterization reports. In addition, possible causes for the witnessed discrepancies need to be addressed toward paving the way for further clinical application and safer practices. The objective of this review is to investigate the marker characterization as well as the potential causes of the discrepancies in the previous reports on placenta-derived amniotic epithelial and mesenchymal stromal cells. The current discrepancies could be potentially due to reasons including passage number and epithelial to mesenchymal transition (EMT), cell heterogeneity, isolation protocols and cross-contamination, the region of cell isolation on placental disk, measuring methods, and gestational age.

Human Amniotic Epithelial Stem Cells: A Promising Seed Cell for Clinical Applications

“…For further clinical application, more research should be directed towards identifying the most suitable isolation markers for hAESC characterization to develop uniform standards. As described in recent study, the gestational age, region of cell isolation on placenta, isolation protocols, cross-contamination, passage number, epithelial-to-mesenchymal transition (EMT), and measuring methods are potential differences in the characterization of hAESCs and hAMSCs [ 185 ]. Alongside the rapid development of biomaterials aiming to support and protect cells being used for therapy, the combination of hAESCs and biomaterials is a promising tissue engineering method with special requirements.…”

Differentiation of Cells Isolated from Afterbirth Tissues into Hepatocyte-Like Cells and Their Potential Clinical Application in Liver Regeneration

“…After the culture of amnion cells with the hepatic differentiation protocol, they expressed high mRNA levels of both fetal and adult hepatocyte markers: AFP, CYP7A1, ALB, and A1AT [85]. It should be noted, that there are discrepancies in the data presented by authors in the literature concerning the pattern of markers expressed by epithelial and mesenchymal afterbirth cells [109,181]. Native human afterbirth cells share some phenotypic features comparable with human hepatic multipotent stem cells (hHpSC) and bipotent hepatoblasts: EpCAM, CK19, CD133 [17,27,35,181], adult multipotent stem cells expressing mesenchymal markers: CD44, CD73, CD90, CD105, CK19, SSEA-4, NANOG, OCT-4 [15,52,66,67,181,[53][54][55][56][57][58][59][60] and adult bipotent hepatic progenitor cells (HPC): DLK-1 [78,184].…”

“…Their advantages include multilineage potential for differentiation, no need for immunosuppression after administration, and no tumor formation in recipient organisms [147,180]. The heterogeneous population of these cells comprises the cells of different stages of differentiation, namely: pluripotent, multipotent, progenitor, and mature cells, characterized by the expression of specific transcription factors and surface markers [181]. The expression of epithelial, or mesenchymal markers, as well as lineage-associated markers of early differentiation, varies among hAEC and afterbirth MSC reflecting their potential to proliferation, self-renewal, and differentiation towards the cells representing three germ lineages.…”

“…Native human afterbirth cells share some phenotypic features comparable with human hepatic multipotent stem cells (hHpSC) and bipotent hepatoblasts: EpCAM, CK19, CD133 [17,27,35,181], adult multipotent stem cells expressing mesenchymal markers: CD44, CD73, CD90, CD105, CK19, SSEA-4, NANOG, OCT-4 [15,52,66,67,181,[53][54][55][56][57][58][59][60] and adult bipotent hepatic progenitor cells (HPC): DLK-1 [78,184]. EpCAM expression, characteristic of hepatoblasts, but not of mesenchymal liver cells, has been confirmed in afterbirth cells only in few studies [181,[183][184][185].…”

Effects of Isorhamnetin in Human Amniotic Epithelial Stem Cells in vitro and Its Cardioprotective Effects in vivo

“…One of the major obstacles of translating hAESCs into the clinic is the heterogeneity in primary amnion epithelial cell population and discrepancies in their cell surface profiling (Centurione et al, 2018) that can be primarily attributed to isolation protocols, gestational age, passage number, and epithelial to mesenchymal transition (Ghamari et al, 2020). However, hAESCs isolated from the adherent subpopulations of passaged primary cells, and cultured in 3D environment may successfully overcome these limitations and may express a higher level of stemness properties (Ferdousi et al, 2019;Furuya et al, 2019).…”