title: Stromal cell-induced immune regulation in a transplantable lymphoid-like cell constructs.
abstract: Engineering of cell-based constructs for treating a variety of immune-related diseases by local transplantation of the cells in a pre-designed matrix is an emerging therapeutic approach, which can potentially reduce the side effects associated with systemic cell injection. Stromal cells have been shown to exert immunosuppressive properties and thus can be exploited for autoimmune regulation and cell transplantation. Here, we demonstrate the fabrication of a stromal cell-based construct, which serves as a lymphoid-like organ with immune regulatory characteristics. In the proposed system, stromal cells are co-seeded with dendritic cells (DC) in a macro-porous alginate scaffold containing the encephalitogenic myelin-derived peptide, proteolipid protein (PLP). We demonstrate that the presence of stromal cells attenuates DC maturation upon lipopolysaccharide stimulus. In vitro, we show that while the migration of pathogenic PLP-specific T cells to construct cultivated with or without stromal cells does not differ, their activation and proliferation are significantly suppressed in the presence of stromal cells. Upon in vivo transplantation, under the kidney capsule of mice, the pathogenic activation and proliferation of T cells which were drawn into the construct were suppressed in the co-seeded constructs. This system thus serves as a lymphoid-like organ with regulatory characteristics, which can be applied for local tolerance induction, for application in cell transplantations as well as autoimmune diseases.
authors.affiliation: Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Kaminer-Israeli
authors.forename: Jenny
authors.initials: J
authors.lastname: Shapiro
authors.forename: Smadar
authors.initials: S
authors.lastname: Cohen
authors.forename: Alon
authors.initials: A
authors.lastname: Monsonego
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005434:Flow Cytometry; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D007108:Immune Tolerance / Q000187:drug effects; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D018991:Myelin Proteolipid Protein / Q000737:chemistry / Q000276:immunology; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology*; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D008070:Lipopolysaccharides; D018991:Myelin Proteolipid Protein; D020723:Glucuronic Acid