Methods and compositions for isolation and growth of kidney tubule stem cells, in vitro kidney tubulogenesis and ex vivo construction of renal tubules
AssigneeUniversity of Michigan
InventorH. David Humes
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Abstract
Methods, including culture media conditions, which provide for isolation and purification of renal tubule stem cells and for in vitro kidney tubulogenesis are disclosed. The methods rely on culturing adult kidney cells in a culture media treated with combinations of transforming growth factor-.beta..sub.1, epidermal growth factor, and all-trans retinoic acid.
Claims16
An ex vivo renal tubule tissue system prepared by a process comprising culturing adult kidney cells in a culture medium comprising all-trans retinoic acid, transforming growth factor-.beta..sub.1 and either epidermal growth factor or transforming growth factor-.alpha. in an amount effective for achieving tubulogenesis, wherein tubulogenesis is a phenotypic transformation of said cells such that condensed aggregates of tubule cells form about a central lumen wherein said lumen is bordered by cells possessing a polarized epithelial phenotype with extensive microvilli formation and tight junctional complexes along the lumenal border.
A method for growing kidney tubule stem cells ex vivo, comprising culturing adult kidney cells in the presence of all-trans retinoic acid, transforming growth factor-.beta..sub.1, and either epidermal growth factor or transforming growth factor-.alpha., in an amount effective for achieving tubulogenesis, wherein tubulogenesis is a phenotypic transformation of said cells such that condensed aggregates of tubule cells form about a central lumen wherein said lumen is bordered by cells possessing a polarized epithelial phenotype with extensive microvilli formation and tight junctional complexes along the lumenal border.
A method for effecting tubulogenesis in a renal cell culture ex vivo, comprising culturing adult kidney cells in the presence of all-trans retinoic acid, transforming growth factor-.beta..sub.1, and either epidermal growth factor or transforming growth factor-.alpha. in an amount effective for achieving tubulogenesis, wherein tubulogenesis is a phenotypic transformation of said cells such that condensed aggregates of tubule cells form about a central lumen wherein said lumen is bordered by cells possessing a polarized epithelial phenotype with extensive microvilli formation and tight junctional complexes along the lumenal border.
A method for constructing and maintaining an ex vivo renal tubule tissue system, comprising culturing adult kidney cells in the presence of all-trans retinoic acid, transforming growth factor-.beta..sub.1, and either epidermal growth factor or transforming growth factor-.alpha. in an amount effective for achieving tubulogenesis, wherein tubulogenesis is aa phenotypic transformation of said cells characterized by condensed aggregates of tubule cells forming about a central lumen wherein said lumen is bordered by cells possessing a polarized epithelial phenotype with extensive microvilli formation and tight junctional complexes along the lumenal border.
Dependencies are inferred from the claim text.