Native thymic extracellular matrix improves in vivo thymic organoid T cell output, and drives in vitro thymic epithelial cell differentiation

Michael Hun, Marco Barsanti, Kahlia Wong, John Ramshaw, Jerome Werkmeister, Ann P. Chidgey

Research output: Contribution to journalArticleResearchpeer-review

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.
Original languageEnglish
Article number145253
Pages (from-to)1-15
Number of pages15
JournalBiomaterials
Volume118
DOIs
Publication statusPublished - Feb 2017

Keywords

  • 3D culture system
  • Decellularized thymus
  • Thymic epithelial cells
  • Thymus
  • Thymus extracellular matrix
  • Thymus organoids
  • Thymus regeneration

Cite this

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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 na{\"i}ve 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 na{\"i}ve 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.",
keywords = "3D culture system, Decellularized thymus, Thymic epithelial cells, Thymus, Thymus extracellular matrix, Thymus organoids, Thymus regeneration",
author = "Michael Hun and Marco Barsanti and Kahlia Wong and John Ramshaw and Jerome Werkmeister and Chidgey, {Ann P.}",
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Native thymic extracellular matrix improves in vivo thymic organoid T cell output, and drives in vitro thymic epithelial cell differentiation. / Hun, Michael; Barsanti, Marco; Wong, Kahlia; Ramshaw, John; Werkmeister, Jerome; Chidgey, Ann P.

In: Biomaterials, Vol. 118, 145253, 02.2017, p. 1-15.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Hun, Michael

AU - Barsanti, Marco

AU - Wong, Kahlia

AU - Ramshaw, John

AU - Werkmeister, Jerome

AU - Chidgey, Ann P.

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