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Pluripotent Stem Cell-Derived Hepatocytes Inhibit T Cell Proliferation In Vitro through Tryptophan Starvation.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Elgueta, Raul 
McCluskey, Daniel 
Ortega-Prieto, Ana Maria  ORCID logo  https://orcid.org/0000-0002-9023-0103
Stolarczyk, Emilie 

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.

Description

Keywords

T cell activation, iPSC-derived hepatocyte-like cells, in vitro studies, regenerative medicine, Allogeneic Cells, Cell Proliferation, Hepatocytes, Humans, Immunologic Factors, Immunophenotyping, Indoleamine-Pyrrole 2,3,-Dioxygenase, Induced Pluripotent Stem Cells, Lymphocyte Activation, Receptors, Antigen, T-Cell, T-Lymphocytes, Tryptophan

Journal Title

Cells

Conference Name

Journal ISSN

2073-4409
2073-4409

Volume Title

11

Publisher

MDPI AG
Sponsorship
Medical Research Council (MR/L022699/1, MR/S020934/1)
Chief Scientist Office (TCS 16/37)