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 Abba Abdulkadir, Gail S. Prins, Larisa Nonn*

*Corresponding author for this work

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)304-317
Number of pages14
JournaliScience
Volume12
DOIs
StatePublished - Feb 22 2019

Fingerprint

Organoids
stromal cells
branching
Prostate
viability
Phenotype
phenotype
Stromal Cells
prostatic neoplasms
coculture
carcinogenesis
growth factors
fibroblasts
epithelial cells
Tissue Survival
Coculture Techniques
Prostatic Neoplasms
Intercellular Signaling Peptides and Proteins
Carcinogenesis
Fibroblasts

Keywords

  • Bioengineering
  • Biological Sciences
  • Cell Biology
  • Tissue Engineering

ASJC Scopus subject areas

  • General

Cite this

Richards, Z., McCray, T., Marsili, J., Zenner, M. L., Manlucu, J. T., Garcia, J., ... Nonn, L. (2019). Prostate Stroma Increases the Viability and Maintains the Branching Phenotype of Human Prostate Organoids. iScience, 12, 304-317. https://doi.org/10.1016/j.isci.2019.01.028
Richards, Zachary ; McCray, Tara ; Marsili, Joseph ; Zenner, Morgan L. ; Manlucu, Jacob T. ; Garcia, Jason ; Kajdacsy-Balla, Andre ; Murray, Marcus ; Voisine, Cindy ; Murphy, Adam B ; Abdulkadir, Sarki Abba ; Prins, Gail S. ; Nonn, Larisa. / Prostate Stroma Increases the Viability and Maintains the Branching Phenotype of Human Prostate Organoids. In: iScience. 2019 ; Vol. 12. pp. 304-317.
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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.",
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Richards, Z, McCray, T, Marsili, J, Zenner, ML, Manlucu, JT, Garcia, J, Kajdacsy-Balla, A, Murray, M, Voisine, C, Murphy, AB, Abdulkadir, SA, Prins, GS & Nonn, L 2019, 'Prostate Stroma Increases the Viability and Maintains the Branching Phenotype of Human Prostate Organoids', iScience, vol. 12, pp. 304-317. https://doi.org/10.1016/j.isci.2019.01.028

Prostate Stroma Increases the Viability and Maintains the Branching Phenotype of Human Prostate Organoids. / Richards, Zachary; McCray, Tara; Marsili, Joseph; Zenner, Morgan L.; Manlucu, Jacob T.; Garcia, Jason; Kajdacsy-Balla, Andre; Murray, Marcus; Voisine, Cindy; Murphy, Adam B; Abdulkadir, Sarki Abba; Prins, Gail S.; Nonn, Larisa.

In: iScience, Vol. 12, 22.02.2019, p. 304-317.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Prostate Stroma Increases the Viability and Maintains the Branching Phenotype of Human Prostate Organoids

AU - Richards, Zachary

AU - McCray, Tara

AU - Marsili, Joseph

AU - Zenner, Morgan L.

AU - Manlucu, Jacob T.

AU - Garcia, Jason

AU - Kajdacsy-Balla, Andre

AU - Murray, Marcus

AU - Voisine, Cindy

AU - Murphy, Adam B

AU - Abdulkadir, Sarki Abba

AU - Prins, Gail S.

AU - Nonn, Larisa

PY - 2019/2/22

Y1 - 2019/2/22

N2 - 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.

AB - 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.

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KW - Cell Biology

KW - Tissue Engineering

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