In vitro reconstitution of human kidney structures for renal cell therapy

Nadia K. Guimaraes-Souza, Liliya M. Yamaleyeva, Tamer Aboushwareb, Anthony Atala, James J. Yoo

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Background. Recent advances in cell therapies have provided potential opportunities for the treatment of chronic kidney diseases (CKDs). We investigated whether human kidney structures could be preformed in vitro for subsequent implantation in vivo to maximize tissue-forming efficiency. Methods. Human renal cells were isolated from unused donor kidneys. Human renal cells were cultured and expanded. Migration was analyzed using growth factors. To form structures, cells were placed in a three-dimensional culture system. Cells were characterized by immunofluorescence, western blots and fluorescence-activated cell sorting using renal cell-specific markers for podocin, proximal and distal tubules and collecting ducts. An albumin uptake assay was used to analyze function. Three-dimensional cultures were implanted into athymic rat kidneys to evaluate survival. Results. Human renal cells were effectively expanded in culture and retained their phenotype, migration ability and albumin uptake functions. Human renal cell in three-dimensional culture-formed tubules, which stained positively for proximal, distal tubule and collecting duct markers, and this was confirmed by western blot. Polarity of the tubular cells was determined by the presence of E-cadherin, N-cadherin and Na-K ATPase. Colocalization of labeled albumin and proximal tubule markers proved functionality and specificity of the newly formed tubules. An in vivo study showed that cells survived in the kidney for up to 6 weeks. Conclusion. sThese findings demonstrate that human renal cell grown in three-dimensional culture are able to generate kidney structures in vitro. This system may ultimately be developed into an efficient cell-based therapy for patients with CKD.

Original languageEnglish (US)
Pages (from-to)3082-3090
Number of pages9
JournalNephrology Dialysis Transplantation
Volume27
Issue number8
DOIs
StatePublished - Aug 1 2012

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Keywords

  • cell therapy
  • chronic kidney disease
  • human renal cells
  • three-dimensional cell culture

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Guimaraes-Souza, N. K., Yamaleyeva, L. M., Aboushwareb, T., Atala, A., & Yoo, J. J. (2012). In vitro reconstitution of human kidney structures for renal cell therapy. Nephrology Dialysis Transplantation, 27(8), 3082-3090. https://doi.org/10.1093/ndt/gfr785