Report of the National Cancer Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development–sponsored workshop: gynecology and women’s health–benign conditions and cancer

Samimi, Goli; Sathyamoorthy, Neeraja; Tingen, Candace; Mazloomdoost, Donna; Conroy, J. D.; Heckman-Stoddard, Brandy M.; Halvorson, Lisa M.

doi:10.1016/j.ajog.2020.08.049

Cited by 10 publications

(11 citation statements)

References 95 publications

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“…Endometriosis research is hindered by the scarcity of representative endometriotic in vitro models [16][17][18][19]. Our study shows that large spheroids generated from 12Z cells represent human endometriosis characteristics and that complex 3D tissue-like constructs can be successfully biofabricated to model endometriosis and the endometriotic microenvironment.…”

Section: Discussionmentioning

confidence: 83%

“…Despite a large number of ovarian cancer cell lines, there are few benign gynecological cell lines modeling diseases such as endometriosis, and even fewer epithelial-like endometriotic cell lines [16][17][18][19]. Therefore, we chose to focus on a commercially available immortalized endometriotic epitheliallike cell line, 12Z, as the epithelial cell for these proof-of-concept models.…”

Section: Discussionmentioning

confidence: 99%

“…The scarcity of representative endometriotic in vitro models hinders research within the endometriosis field [16][17][18][19]. Immortalized stromal cell lines have been developed from endometrial tissue from women with endometriosis or endometriotic lesions [20,21].…”

Section: Introductionmentioning

confidence: 99%

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Three-Dimensional Biofabrication Models of Endometriosis and the Endometriotic Microenvironment

Wendel¹,

Wang²,

Smith³

et al. 2020

Preprint

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Endometriosis occurs when endometrial-like tissue grows outside the uterine cavity, leading to pelvic pain, infertility, and increased risk of ovarian cancer. The present study describes the optimization and characterization of cellular spheroids as building blocks for Kenzan scaffold-free method biofabrication and proof-of-concept models of endometriosis and the endometriotic microenvironment. The spheroid building blocks must be a specific diameter (~500 m), compact, round, and smooth to withstand Kenzan biofabrication. Under optimized spheroid conditions for biofabrication, the endometriotic epithelial-like cell line, 12Z, expressed high levels of estrogen-related genes and secreted high amounts of endometriotic inflammatory factors that were independent of TNF stimulation. Heterotypic spheroids, composed of 12Z and T-HESC, an immortalized endometrial stromal cell line, self-assembled into a biologically relevant pattern, consisting of epithelial cells on the outside of the spheroids and stromal cells in the core. 12Z spheroids were biofabricated into large three-dimensional constructs alone, with HEYA8 spheroids, or as heterotypic spheroids with T-HESC. These three-dimensional biofabricated constructs containing multiple monotypic or heterotypic spheroids represent the first scaffold-free biofabricated in vitro models of endometriosis and the endometriotic microenvironment. These efficient and innovative models will allow us to study the complex interactions of multiple cell types within a biologically relevant microenvironment.

show abstract

Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Three-Dimensional Biofabrication Models of Endometriosis and the Endometriotic Microenvironment

Wendel¹,

Wang²,

Smith³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Endometriosis research is hindered by the scarcity of representative endometriotic in vitro models [ 16 , 17 , 18 , 19 ]. Our study shows that large spheroids generated from 12Z cells represent specific human endometriosis characteristics better than monolayer culture.…”

Section: Discussionmentioning

confidence: 99%

“…The scarcity of representative endometriotic in vitro models hinders research within the endometriosis field [ 16 , 17 , 18 , 19 ]. Immortalized stromal cell lines have been developed from endometrial tissue from women with endometriosis or endometriotic lesions [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Three-Dimensional Biofabrication Models of Endometriosis and the Endometriotic Microenvironment

et al. 2020

View full text Add to dashboard Cite

Endometriosis occurs when endometrial-like tissue grows outside the uterine cavity, leading to pelvic pain, infertility, and increased risk of ovarian cancer. The present study describes the optimization and characterization of cellular spheroids as building blocks for Kenzan scaffold-free method biofabrication and proof-of-concept models of endometriosis and the endometriotic microenvironment. The spheroid building blocks must be of a specific diameter (~500 μm), compact, round, and smooth to withstand Kenzan biofabrication. Under optimized spheroid conditions for biofabrication, the endometriotic epithelial-like cell line, 12Z, expressed high levels of estrogen-related genes and secreted high amounts of endometriotic inflammatory factors that were independent of TNFα stimulation. Heterotypic spheroids, composed of 12Z and T-HESC, an immortalized endometrial stromal cell line, self-assembled into a biologically relevant pattern, consisting of epithelial cells on the outside of the spheroids and stromal cells in the core. 12Z spheroids were biofabricated into large three-dimensional constructs alone, with HEYA8 spheroids, or as heterotypic spheroids with T-HESC. These three-dimensional biofabricated constructs containing multiple monotypic or heterotypic spheroids represent the first scaffold-free biofabricated in vitro models of endometriosis and the endometriotic microenvironment. These efficient and innovative models will allow us to study the complex interactions of multiple cell types within a biologically relevant microenvironment.

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The independent and joint associations of hysterectomy and uterine fibroids or endometriosis with ovarian cancer incidence: results from a US-based cohort

Tekle,

Sandler,

Ogunsina

et al. 2024

American Journal of Epidemiology

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Uterine fibroids and endometriosis may be associated with an increased risk of ovarian cancer. Less is known about the role of hysterectomy in these associations. We estimated the independent and joint associations of hysterectomy, fibroids, and endometriosis with ovarian cancer incidence in the prospective Sister Study cohort (2003-2009). We used time-varying Cox proportional hazards models to estimate covariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). By the end of follow-up, 34% of 40,928 eligible participants had fibroids, 13% had endometriosis, and 7% had both. A total of 274 women developed ovarian cancer during follow-up (median=12.3 years). In mutually adjusted models, fibroids (HR=1.65, 95% CI: 1.28, 2.12) and possibly endometriosis (HR=1.16, 95% CI: 0.82, 1.63), were positively associated with ovarian cancer. Hysterectomies (20% of participants) were also positively associated with ovarian cancer (HR=1.29, 95% CI: 0.95, 1.74). There was some evidence that hysterectomies may mitigate ovarian cancer risk among women with fibroids (HR=0.83, 95% CI: 0.56, 1.24), but not among women with endometriosis (HR=1.20, 95% CI: 0.65, 2.22). Identifying these joint associations adds to our understanding of ovarian cancer etiology and may help inform decisions about how women with fibroids, endometriosis, and hysterectomies are treated and surveilled for ovarian cancer.

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Report of the National Cancer Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development–sponsored workshop: gynecology and women’s health–benign conditions and cancer

Cited by 10 publications

References 95 publications

Three-Dimensional Biofabrication Models of Endometriosis and the Endometriotic Microenvironment

Three-Dimensional Biofabrication Models of Endometriosis and the Endometriotic Microenvironment

Three-Dimensional Biofabrication Models of Endometriosis and the Endometriotic Microenvironment

The independent and joint associations of hysterectomy and uterine fibroids or endometriosis with ovarian cancer incidence: results from a US-based cohort

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