Prostate Stroma Increases the Viability and Maintains the Branching Phenotype of Human Prostate Organoids

Autor: Zachary Richards, Tara McCray, Joseph Marsili, Morgan L. Zenner, Jacob T. Manlucu, Jason Garcia, Andre Kajdacsy-Balla, Marcus Murray, Cindy Voisine, Adam B. Murphy, Sarki A. Abdulkadir, Gail S. Prins, Larisa Nonn
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: iScience, Vol 12, Iss , Pp 304-317 (2019)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2019.01.028
Popis: Summary: The fibromuscular stroma of the prostate regulates normal epithelial differentiation and contributes to carcinogenesis in vivo. We developed and characterized a human 3D prostate organoid co-culture model that incorporates prostate stroma. Primary prostate stromal cells increased organoid formation and directed organoid morphology into a branched acini structure similar to what is observed in vivo. Organoid branching occurred distal to physical contact with stromal cells, demonstrating non-random branching. Stroma-induced phenotypes were similar in all patients examined, yet they maintained inter-patient heterogeneity in the degree of response. Stromal cells expressed growth factors involved in epithelial differentiation, which was not observed in non-prostatic fibroblasts. Organoids derived from areas of prostate cancer maintained differential expression of alpha-methylacyl-CoA racemase and showed increased viability and passaging when co-cultured with stroma. The addition of stroma to epithelial cells in vitro improves the ability of organoids to recapitulate features of the tissue and enhances the viability of organoids. : Bioengineering; Biological Sciences; Cell Biology; Tissue Engineering Subject Areas: Bioengineering, Biological Sciences, Cell Biology, Tissue Engineering
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