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 language | English (US) |
|---|---|
| Pages (from-to) | 304-317 |
| Number of pages | 14 |
| Journal | iScience |
| Volume | 12 |
| DOIs | |
| State | Published - Feb 22 2019 |
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Keywords
- Bioengineering
- Biological Sciences
- Cell Biology
- Tissue Engineering
ASJC Scopus subject areas
- General
Cite this
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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 journal › Article
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.
KW - Bioengineering
KW - Biological Sciences
KW - Cell Biology
KW - Tissue Engineering
UR - http://www.scopus.com/inward/record.url?scp=85066247313&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85066247313&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2019.01.028
DO - 10.1016/j.isci.2019.01.028
M3 - Article
C2 - 30735898
AN - SCOPUS:85066247313
VL - 12
SP - 304
EP - 317
JO - iScience
JF - iScience
SN - 2589-0042
ER -