Abstract
Regenerative medicine aims to replace damaged tissues by stimulating endogenous tissue repair or by transplanting autologous or allogeneic cells. Due to their capacity to produce unlimited numbers of cells of a given cell type, pluripotent stem cells, whether of embryonic origin or induced via the reprogramming of somatic cells, are of considerable therapeutic interest in the regenerative medicine field. However, regardless of the cell type, host immune responses present a barrier to success. The aim of this study was to investigate in vitro the immunological properties of human pluripotent stem cell (PSC)-derived hepatocyte-like cells (HLCs). These cells expressed MHC class I molecules while they lacked MHC class II and co-stimulatory molecules, such as CD80 and CD86. Following stimulation with IFN-γ, HLCs upregulated CD40, PD-L1 and MHC class I molecules. When co-cultured with allogeneic T cells, HLCs did not induce T cell proliferation; furthermore, when T cells were stimulated via αCD3/CD28 beads, HLCs inhibited their proliferation via IDO1 and tryptophan deprivation. These results demonstrate that PSC-derived HLCs possess immunoregulatory functions, at least in vitro.
Highlights
Transplantation is the treatment of choice for many end-stage organs, such as the liver.organ rejection and long-term immunosuppression present a real challenge, and new strategies are needed [1]
In order to understand the immunogenicity of induced pluripotent stem cells (iPSCs)-hepatocyte-like cells (HLCs), we first evaluated whether specific markers of hepatocellular differentiation were maintained on HCLs in a proinflammatory microenvironment
HNF4a and SERPINA gene expression in HLCs were similar to adult hepatocytes (Figure 1A,B), while undifferentiated iPSCs were negative for the expression of these two genes (Figure 1A,B)
Summary
Transplantation is the treatment of choice for many end-stage organs, such as the liver.organ rejection and long-term immunosuppression present a real challenge, and new strategies are needed [1]. One alternative strategy is the transplantation of allogeneic adult hepatocytes, which has been pioneered to reduce the severity of congenital errors of liver metabolism and chronic/acute failure to act as a bridge until the organ becomes available [2]. In both animals and humans, sustained liver function following hepatocytes’ transplantation has not been achieved [3]. Hepatocytes from renewable and immune matched sources, such as pluripotent stem cells (PSCs), have been proposed as a concrete alternative to primary human hepatocytes to support organ function and regeneration
Sign-in/Register to view highlights & summary 
Published Version (
Free)
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.
