title: Construction of Thymus Organoids from Decellularized Thymus Scaffolds.
abstract: One of the hallmarks of modern medicine is the development of therapeutics that can modulate immune responses, especially the adaptive arm of immunity, for disease intervention and prevention. While tremendous progress has been made in the past decades, manipulating the thymus, the primary lymphoid organ responsible for the development and education of T lymphocytes, remains a challenge. One of the major obstacles is the difficulty to reproduce its unique extracellular matrix (ECM) microenvironment that is essential for maintaining the function and survival of thymic epithelial cells (TECs), the predominant population of cells in the thymic stroma. Here, we describe the construction of functional thymus organoids from decellularized thymus scaffolds repopulated with isolated TECs. Thymus decellularization was achieved by freeze-thaw cycles to induce intracellular ice crystal formation, followed by detergent-induced cell lysis. Cellular debris was removed with extensive wash. The decellularized thymus scaffolds can largely retain the 3D extracellular matrix (ECM) microenvironment that can support the recolonization of TECs. When transplanted into athymic nude mice, the reconstructed thymus organoids can effectively promote the homing of bone marrow-derived lymphocyte progenitors and support the development of a diverse and functional T cell repertoire. Bioengineering of thymus organoids can be a promising approach to rejuvenate/modulate the function of T-cell mediated adaptive immunity in regenerative medicine.
authors.affiliation: Institute of Cellular Therapeutics, Allegheny Health Network, Pittsburgh, PA, USA.
authors.forename: Asako
authors.initials: A
authors.lastname: Tajima
authors.affiliation: Institute of Cellular Therapeutics, Allegheny Health Network, Pittsburgh, PA, USA.
authors.forename: Isha
authors.initials: I
authors.lastname: Pradhan
authors.affiliation: Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Xuehui
authors.initials: X
authors.lastname: Geng
authors.affiliation: Institute of Cellular Therapeutics, Allegheny Health Network, Pittsburgh, PA, USA.|Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA.|Department of Microbiology and Immunology, Medical College of Drexel University, Philadelphia, PA, USA.
authors.forename: Massimo
authors.initials: M
authors.lastname: Trucco
authors.affiliation: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA. yong.fan74@gmail.com.|Department of Microbiology and Immunology, Medical College of Drexel University, Philadelphia, PA, USA. yong.fan74@gmail.com.|Institute of Cellular Therapeutics, Allegheny Health Network, Room 1107 South Tower, 320 East North Avenue, Pittsburgh, PA, 15212, USA. yong.fan74@gmail.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Fan
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D002478:Cells, Cultured; D005109:Extracellular Matrix; D051379:Mice; D008819:Mice, Nude; D009940:Organoids / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
keywords: Decellularization; Organoids; Scaffold; Thymus; Tissue engineering