In vivo genetic selection of renal proximal tubules

Patrice K. Held, Muhsen Al-Dhalimy, Holger Willenbring, Yassmine Akkari, Shuguang Jiang, Yumi Torimaru, Susan Olson, William Fleming, Milton Finegold, Markus Grompe

Research output: Contribution to journalArticle

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Abstract

Repopulation by transplanted cells can result in effective therapy for several regenerative organs including blood, liver, and skin. In contrast, cell therapies for renal diseases are not currently available. Here we developed an animal model in which cells genetically resistant to a toxic intermediate of tyrosine metabolism, homogentisic acid (HGA), were able to repopulate the damaged proximal tubule epithelium of mice with fumarylacetoacetate hydrolase (Fah) deficiency. HGA resistance was achieved by two independent mechanisms. First, Fah+ transplanted bone marrow cells produced significant replacement of damaged proximal tubular epithelium (up to 50%). The majority of bone marrow-derived epithelial cells were generated by cell fusion, not transdifferentiation. In addition to regeneration by fusion-derived epithelial cells, proximal tubular repopulation was also observed by host epithelial cells, which had lost the homogentisic acid dioxygenase gene. These data demonstrate that extensive regeneration of the renal proximal tubule compartment can be achieved through genetic selection of functional cells.

Original languageEnglish (US)
Pages (from-to)49-58
Number of pages10
JournalMolecular Therapy
Volume13
Issue number1
DOIs
StatePublished - Jan 2006

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Homogentisic Acid
Proximal Kidney Tubule
Genetic Selection
Epithelial Cells
Regeneration
Epithelium
Dioxygenases
Cell Fusion
Poisons
Cell- and Tissue-Based Therapy
Bone Marrow Cells
Tyrosine
Animal Models
Bone Marrow
Kidney
Skin
Liver
Genes
fumarylacetoacetase
Therapeutics

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Held, P. K., Al-Dhalimy, M., Willenbring, H., Akkari, Y., Jiang, S., Torimaru, Y., ... Grompe, M. (2006). In vivo genetic selection of renal proximal tubules. Molecular Therapy, 13(1), 49-58. https://doi.org/10.1016/j.ymthe.2005.09.004

In vivo genetic selection of renal proximal tubules. / Held, Patrice K.; Al-Dhalimy, Muhsen; Willenbring, Holger; Akkari, Yassmine; Jiang, Shuguang; Torimaru, Yumi; Olson, Susan; Fleming, William; Finegold, Milton; Grompe, Markus.

In: Molecular Therapy, Vol. 13, No. 1, 01.2006, p. 49-58.

Research output: Contribution to journalArticle

Held, PK, Al-Dhalimy, M, Willenbring, H, Akkari, Y, Jiang, S, Torimaru, Y, Olson, S, Fleming, W, Finegold, M & Grompe, M 2006, 'In vivo genetic selection of renal proximal tubules', Molecular Therapy, vol. 13, no. 1, pp. 49-58. https://doi.org/10.1016/j.ymthe.2005.09.004
Held PK, Al-Dhalimy M, Willenbring H, Akkari Y, Jiang S, Torimaru Y et al. In vivo genetic selection of renal proximal tubules. Molecular Therapy. 2006 Jan;13(1):49-58. https://doi.org/10.1016/j.ymthe.2005.09.004
Held, Patrice K. ; Al-Dhalimy, Muhsen ; Willenbring, Holger ; Akkari, Yassmine ; Jiang, Shuguang ; Torimaru, Yumi ; Olson, Susan ; Fleming, William ; Finegold, Milton ; Grompe, Markus. / In vivo genetic selection of renal proximal tubules. In: Molecular Therapy. 2006 ; Vol. 13, No. 1. pp. 49-58.
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