Improved structure and function in autosomal recessive polycystic rat kidneys with renal tubular cell therapy

Katherine Kelly, Jizhong Zhang, Ling Han, Malgorzata Kamocka, Caroline Miller, Vincent H. Gattone, Jesus Dominguez

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1mRNA.

Original languageEnglish
Article numbere0131677
JournalPLoS One
Volume10
Issue number7
DOIs
StatePublished - Jul 2 2015

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Autosomal Recessive Polycystic Kidney
kidney cells
Cell- and Tissue-Based Therapy
Rats
kidneys
Kidney
therapeutics
rats
exosomes
cells
Exosomes
Polycystic Kidney Diseases
Kidney Transplantation
phenotype
mutants
cell transplantation
disease models
renal function
amyloid
Phenotype

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Improved structure and function in autosomal recessive polycystic rat kidneys with renal tubular cell therapy. / Kelly, Katherine; Zhang, Jizhong; Han, Ling; Kamocka, Malgorzata; Miller, Caroline; Gattone, Vincent H.; Dominguez, Jesus.

In: PLoS One, Vol. 10, No. 7, e0131677, 02.07.2015.

Research output: Contribution to journalArticle

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