Xenotransplantation. 2017 Jan 19. doi: 10.1111/xen.12287. [Epub ahead of print]

Immunogenicity of hepatic differentiated human umbilical cord mesenchymal stem cells promoted by porcine decellularized liver scaffolds.

Li Y^1,2,3, Wu Q^1,2, Wang Y^1,2,3, Li L^1,2, Chen F^1,2, Shi Y^1,2, Bu H^1,2,4, Bao J^1,2.

Abstract

Cell-based approaches, including hepatocyte transplantation and tissue-engineered livers, offer promising alternatives and are expected to help support patients with liver diseases until liver transplantation or recovery via regeneration of the damaged liver. However, the success of cell therapies remains dependent on how well the cells are accepted after transplantation and is directly related to their degree of immunogenicity. In this study, hepatic differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) was induced in the traditional monolayer (2D) culture and newly established three-dimensional (3D) aggregation culture with the porcine decellularized liver scaffold (DLS) system (3D-DLS). We investigated the immunogenicity of these hepatocyte-like cells in vitro. We found that monolayer hepatic differentiated hUC-MSCs expressed higher levels of human leukocyte antigen-DR (HLA-DR) (P<.05) and lost the ability to inhibit lymphocyte proliferation (P<.05), in association with a lower level of prostaglandin E₂ (PGE₂ ) (P<.05) and a higher level of interferon-γ (IFN-γ) (P<.05) secretion, compared to undifferentiated hUC-MSCs. The hepatocyte-like cells differentiated in the 3D-DLS system did not show an elevation of MHC-II (P>.05), or cause obvious lymphocytes proliferation, and demonstrated more PGE₂ (P<.05) and less IFN-γ (P<.05) secretion. Hepatocyte-like cells in the 3D-DLS system presented a lower immunogenic phenotype than the 2D culture in vitro. Hepatocyte-like cells in 3D-DLS system also performed a higher immunosuppressive capacity than 2D culture.