Three dimensional culture of human renal cell carcinoma organoids

Cynthia A. Batchelder, Michele L. Martinez, Nadire Duru, Frederick J Meyers, Alice F Tarantal

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Renal cell carcinomas arise from the nephron but are heterogeneous in disease biology, clinical behavior, prognosis, and response to systemic therapy. Development of patientspecific in vitro models that efficiently and faithfully reproduce the in vivo phenotype may provide a means to develop personalized therapies for this diverse carcinoma. Studies to maintain and model tumor phenotypes in vitro were conducted with emerging three-dimensional culture techniques and natural scaffolding materials. Human renal cell carcinomas were individually characterized by histology, immunohistochemistry, and quantitative PCR to establish the characteristics of each tumor. Isolated cells were cultured on renal extracellular matrix and compared to a novel polysaccharide scaffold to assess cell-scaffold interactions, development of organoids, and maintenance of gene expression signatures over time in culture. Renal cell carcinomas cultured on renal extracellular matrix repopulated tubules or vessel lumens in renal pyramids and medullary rays, but cells were not observed in glomeruli or outer cortical regions of the scaffold. In the polysaccharide scaffold, renal cell carcinomas formed aggregates that were loosely attached to the scaffold or free-floating within the matrix. Molecular analysis of cell-scaffold constructs including immunohistochemistry and quantitative PCR demonstrated that individual tumor phenotypes could be sustained for up to 21 days in culture on both scaffolds, and in comparison to outcomes in two-dimensional monolayer cultures. The use of three-dimensional scaffolds to engineer a personalized in vitro renal cell carcinoma model provides opportunities to advance understanding of this disease.

Original languageEnglish (US)
Article numbere0136758
JournalPLoS One
Volume10
Issue number8
DOIs
StatePublished - Aug 28 2015

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Organoids
kidney cells
Renal Cell Carcinoma
Cell culture
Scaffolds
carcinoma
Cells
Phenotype
Kidney
kidneys
Extracellular Matrix
Polysaccharides
phenotype
extracellular matrix
Tumors
neoplasms
Immunohistochemistry
immunohistochemistry
quantitative polymerase chain reaction
polysaccharides

ASJC Scopus subject areas

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

Cite this

Three dimensional culture of human renal cell carcinoma organoids. / Batchelder, Cynthia A.; Martinez, Michele L.; Duru, Nadire; Meyers, Frederick J; Tarantal, Alice F.

In: PLoS One, Vol. 10, No. 8, e0136758, 28.08.2015.

Research output: Contribution to journalArticle

Batchelder, Cynthia A. ; Martinez, Michele L. ; Duru, Nadire ; Meyers, Frederick J ; Tarantal, Alice F. / Three dimensional culture of human renal cell carcinoma organoids. In: PLoS One. 2015 ; Vol. 10, No. 8.
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