title: Native thymic extracellular matrix improves in vivo thymic organoid T cell output, and drives in vitro thymic epithelial cell differentiation.
abstract: Although the thymus is a primary lymphoid organ, its function is compromised by an age-induced loss of resident epithelial cells, which results in reduced naïve T cell output. This has important implications for immune recovery in aged and elderly patients following damage from cytoablative therapies. As thymic architecture plays a crucial role in naïve T cell development, a tissue specific scaffold that provides essential supporting matrix may assist in stem cell-based thymus regeneration to recreate complex organoids. Here we investigate thymus decellularization approaches that preserve major extracellular matrix components and support thymic epithelial cells for the generation of a functional thymic microenvironment with improved T cell output. We also established an in vitro, serum-free culture system that both maintains a progenitor thymic epithelial cell pool and drives their differentiation in the presence of decellularized thymic matrix. This approach enables further dissection of key cellular and niche components involved in thymic epithelial stem cell maintenance and T cell production.
authors.affiliation: Stem Cells and Immune Regeneration Laboratory, Department of Anatomy and Developmental Biology, Level 3, 15 Innovation Walk, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Hun
authors.affiliation: Stem Cells and Immune Regeneration Laboratory, Department of Anatomy and Developmental Biology, Level 3, 15 Innovation Walk, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Marco
authors.initials: M
authors.lastname: Barsanti
authors.affiliation: Stem Cells and Immune Regeneration Laboratory, Department of Anatomy and Developmental Biology, Level 3, 15 Innovation Walk, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Kahlia
authors.initials: K
authors.lastname: Wong
authors.affiliation: CSIRO Manufacturing, Clayton, Victoria 3168, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Ramshaw
authors.affiliation: CSIRO Manufacturing, Clayton, Victoria 3168, Australia.
authors.forename: Jerome
authors.initials: J
authors.lastname: Werkmeister
authors.affiliation: Stem Cells and Immune Regeneration Laboratory, Department of Anatomy and Developmental Biology, Level 3, 15 Innovation Walk, Monash University, Clayton, Victoria 3800, Australia. Electronic address: ann.chidgey@monash.edu.
authors.forename: Ann P
authors.initials: AP
authors.lastname: Chidgey
mesh_terms: D000818:Animals; D021522:Bioartificial Organs; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002474:Cell-Free System; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D005109:Extracellular Matrix / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D009924:Organ Culture Techniques; D038081:Organogenesis / Q000502:physiology; D009940:Organoids / Q000166:cytology / Q000254:growth & development*; D013601:T-Lymphocytes / Q000166:cytology* / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology* / Q000254:growth & development*; D023822:Tissue Engineering; D054457:Tissue Scaffolds
keywords: 3D culture system; Decellularized thymus; Thymic epithelial cells; Thymus; Thymus extracellular matrix; Thymus organoids; Thymus regeneration