title: Characterizing natural hydrogel for reconstruction of three-dimensional lymphoid stromal network to model T-cell interactions.
abstract: Hydrogels have been used in regenerative medicine because they provide a three-dimensional environment similar to soft tissues, allow diffusion of nutrients, present critical biological signals, and degrade via endogenous enzymatic mechanisms. Herein, we developed in vitro system mimicking cell-cell and cell-matrix interactions in secondary lymphoid organs (SLOs). Existing in vitro culture systems cannot accurately represent the complex interactions happening between T-cells and stromal cells in immune response. To model T-cell interaction in SLOs in vitro, we encapsulated stromal cells in fibrin, collagen, or fibrin-collagen hydrogels and studied how different mechanical and biological properties affect stromal network formation. Overall, fibrin supplemented with aprotinin was superior to collagen and fibrin-collagen in terms of network formation and promotion of T-cell penetration. After 8 days of culture, stromal networks formed through branching and joining with other adjacent cell populations. T-cells added to the newly formed stromal networks migrated and attached to stromal cells, similar to the T-cell zones of the lymph nodes in vivo. Our results suggest that the constructed three-dimensional lymphoid stromal network can mimic the in vivo environment and allow the modeling of T-cell interaction in SLOs.
authors: Department of Macromolecular Science and Engineering, University of Michigan, Ann Arbor, Michigan.
authors: Jiwon
authors: J
authors: Kim
authors: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
authors: Biming
authors: B
authors: Wu
authors: Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan.
authors: Steven M
authors: SM
authors: Niedzielski
authors: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
authors: Matthew T
authors: MT
authors: Hill
authors: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
authors: Rhima M
authors: RM
authors: Coleman
authors: Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan.
authors: Akira
authors: A
authors: Ono
authors: Department of Macromolecular Science and Engineering, University of Michigan, Ann Arbor, Michigan.|Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
authors: Ariella
authors: A
authors: Shikanov
mesh_terms: D006801:Humans; D020100:Hydrogels; D017154:Stromal Cells / Q000166:cytology*; D013601:T-Lymphocytes / Q000166:cytology*
chemical_list: D020100:Hydrogels
keywords: fibrin; natural hydrogels; secondary lymphoid organs; stromal network; three-dimensional (3D) cell culture
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