The human placenta is an important source of stem cells that can be easily collected without ethical concerns since it is usually discarded after childbirth. In this study, we analyzed the amniotic membrane (AM) from the human placenta with the aim of mapping different regions with respect to their morpho-functional features and regenerative potential. AMs were obtained from 24 healthy women, undergoing a caesarean section, and mapped into 4 different regions according to their position in relation to the umbilical cord: the central, intermediate, peripheral, and reflected areas. We carried out a multiparametric analysis focusing our attention on amniotic epithelial cells (AECs). Our results revealed that AECs, isolated from the different areas, are a heterogeneous cell population with different pluripotency and proliferation marker expression (octamer-binding transcription factor 4 [OCT-4], tyrosine-protein kinase KIT [c-KIT], sex determining region Y-box 2 [SOX-2], α-fetoprotein, cyclic AMP response element binding [CREB] protein, and phosphorylated active form of CREB [p-CREB]), proliferative ability, and osteogenic potential. Our investigation discloses interesting findings that could be useful for increasing the efficiency of AM isolation and application for therapeutic purposes.

Human Amniotic Epithelial Cells (hAEC) isolated from term placenta are a promising source for regenerative medicine. However, it has long been debated whether the hAEC population consists of heterogeneous or homogeneous cells. In a previous study, we investigated the characteristics of hAEC isolated from four different regions of the amniotic membrane finding significant heterogeneity. The aim of this study was to evaluate the hepatic differentiation capability of hAEC isolated from these four regions. Human term placentae were collected after caesarean section and hAEC were isolated from four regions of the amniotic membrane (R1‐R4, according to their relative distance from the umbilical cord) and treated in hepatic differentiation conditions for 14 days. hAEC‐derived hepatocyte‐like cells showed marked differences in the expression of hepatic markers: R4 showed higher levels of Albumin and Hepatocyte Nuclear Factor (HNF) 4α whereas R1 expressed higher Cytochrome P450 enzymes, both at the gene and protein level. These preliminary results suggest that hAEC isolated from R1 and R4 of the amniotic membrane are more prone to hepatic differentiation. Therefore, the use of hAEC from a specific region of the amniotic membrane should be taken into consideration as it could have an impact on the outcome of therapeutic applications.

The potential clinical applications of human amniotic membrane (hAM) and human amniotic epithelial cells (hAECs) in the field of regenerative medicine have been known in literature since long. However, it has yet to be elucidated whether hAM contains different anatomical regions with different plasticity and differentiation potential. Recently, for the first time, we highlighted many differences in terms of morphology, marker expression, and differentiation capabilities among four distinct anatomical regions of hAM, demonstrating peculiar functional features in hAEC populations. The aim of this study was to investigate in situ the ultrastructure of the four different regions of hAM by means of transmission electron microscopy (TEM) to deeply understand their peculiar characteristics and to investigate the presence and localization of secretory products because to our knowledge, there are no similar studies in the literature. The results of this study confirm our previous observations of hAM heterogeneity and highlight for the first time that hAM can produce extracellular vesicles (EVs) in a heterogeneous manner. These findings should be considered to increase efficiency of hAM applications within a therapeutic context.

In the framework of space flight, the risk of radiation carcinogenesis is considered a “red” risk due to the high likelihood of occurrence as well as the high potential impact on the quality of life in terms of disease-free survival after space missions. The cyclic AMP response element-binding protein (CREB) is overexpressed both in haematological malignancies and solid tumours and its expression and function are modulated following irradiation. The CREB protein is a transcription factor and member of the CREB/activating transcription factor (ATF) family. As such, it has an essential role in a wide range of cell processes, including cell survival, proliferation, and differentiation. Among the CREB-related nuclear transcription factors, NF-κB and p53 have a relevant role in cell response to ionising radiation. Their expression and function can decide the fate of the cell by choosing between death or survival. The aim of this review was to define the role of the CREB/ATF family members and the related transcription factors in the response to ionising radiation of human haematological malignancies and solid tumours.

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