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

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

doi:10.1016/j.isci.2019.01.028

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

iScience. 2019 Feb 22:12:304-317. doi: 10.1016/j.isci.2019.01.028. Epub 2019 Jan 23.

Authors

Affiliations

¹ Department of Pathology, University of Illinois at Chicago, 840 S Wood St., Chicago, IL 60612, USA.
² Department of Pathology, University of Illinois at Chicago, 840 S Wood St., Chicago, IL 60612, USA; Department of Biology, Northeastern Illinois University, Chicago, IL 60625, USA.
³ Department of Biology, Northeastern Illinois University, Chicago, IL 60625, USA.
⁴ Department of Pathology, University of Illinois at Chicago, 840 S Wood St., Chicago, IL 60612, USA; University of Illinois Cancer Center, Chicago, IL 60612, USA.
⁵ Project Brotherhood, Chicago, IL 60637, USA.
⁶ Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
⁷ Department of Pathology, University of Illinois at Chicago, 840 S Wood St., Chicago, IL 60612, USA; Departments of Urology, Physiology, and Biophysics, University of Illinois at Chicago, Chicago, IL 60612, USA; University of Illinois Cancer Center, Chicago, IL 60612, USA.
⁸ Department of Pathology, University of Illinois at Chicago, 840 S Wood St., Chicago, IL 60612, USA; University of Illinois Cancer Center, Chicago, IL 60612, USA. Electronic address: lnonn@uic.edu.

Abstract

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.

Keywords: Bioengineering; Biological Sciences; Cell Biology; Tissue Engineering.

Abstract

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