Abstract
The immunoprivilege status characteristic of human amnion epithelial cells (hAECs) has been recently highlighted in the context of xenogenic transplantation. However, the mechanism(s) involved in such regulatory functions have been so far only partially been clarified. Here, we have analyzed the expression of HLA-Ib molecules in isolated hAEC obtained from full term placentae. Moreover, we asked whether these molecules are involved in the immunoregulatory functions of hAEC. Human amnion-derived cells expressed surface HLA-G and HLA-F at high levels, whereas the commonly expressed HLA-E molecule has been measured at a very low level or null on freshly isolated cells. HLA-Ib molecules can be expressed as membrane-bound and soluble forms, and in all hAEC batches analyzed we measured high levels of sHLA-G and sHLA-E when hAEC were maintained in culture, and such a release was time-dependent. Moreover, HLA-G was present in extracellular vesicles (EVs) released by hAEC. hAEC suppressed T cell proliferation in vitro at different hAEC:T cell ratios, as previously reported. Moreover, inhibition of T cell proliferation was partially reverted by pretreating hAEC with anti-HLA-G, anti-HLA-E and anti-β2 microglobulin, thus suggesting that HLA-G and -E molecules are involved in hAEC-mediated suppression of T cell proliferation. Finally, either large-size EV (lsEV) or small-size EV (ssEV) derived from hAEC significantly modulated T-cell proliferation. In conclusion, we have here characterized one of the mechanism(s) underlying immunomodulatory functions of hAEC, related to the expression and release of HLA-Ib molecules.
Highlights
The human placenta is a complex organ, whose role in regenerative medicine applications have been largely proposed and is gaining interest worldwide
Products isolated from different donors,from anddifferent we consistently we evaluated the expression of HLA molecules on Human amnion epithelial cells (hAECs) derived donors
Since the mechanism(s) underlying these immunoregulatory properties of hAEC have been only partially elucidated [55], we focused on investigating the role of HLA-Ib molecules
Summary
The human placenta is a complex organ, whose role in regenerative medicine applications have been largely proposed and is gaining interest worldwide. Cells 2020, 9, 2123 and fetal tissues, with the latest as a source of multipotent stem cells successfully employed in innovative biomedical approaches [1]. Distinctive is the surface expression of embryonic stem cell markers, such as globoseries glycolipids (SSEA-3 and -4) and keratansulfate associated antigens (TRA 1-60 and 1-81) in hAEC [3,4,5]. AECs have been proved safe and non-tumorigenic upon transplantation, with a normal karyotype, lack of telomerase and limited growing potential in culture [5,6]. These features differentiate hAECs from pluripotent stem cells and support their use in cell-based therapies. Amnion epithelial cells have shown efficacy in different clinical and preclinical trials, representing a promising therapeutic approach in life-threatening models of inborn error of diseases and respiratory distress [7,8,9,10,11]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
