Role of Senescent Cells in Uterine Fibroid Pathogenesis (SOUL Study)

Study Overview
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Brief Summary
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The investigators are evaluating the role of senescent cells in uterine fibroids.

Detailed Description
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Uterine fibroids are prevalent tumors of uterus characterized by excessive fibrotic tissues. Using new cutting-edge computational methods, the investigators have found that small groups of senescent cells in fibroids work in concert with immune cells to produce soluble factors in fibroid tissues to create a feed-forward loop leading to fibrosis. This project seeks to unravel key cell-cell communication networks involving senescent and immune cells in fibroids to develop new treatments for uterine fibroids.

Official Title
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Role of Senescent Cells in Uterine Fibroid Pathogenesis

Conditions
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Fibroid, Leiomyoma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must be women above the age of ≥18 - ≤55 years. Women with suspected uterine fibroids. Subject must be or have been sexually active or have had a previous vaginal exam that used a speculum. Subject must be able to understand, read and speak English or Spanish and subsequently, be able to understand what she is consenting to in terms of procedures and use/disclosure of protected health information. Exclusion Criteria: Unwilling to sign the consent form or complete questionnaire. Pregnancy. Cancer of the uterus

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Women with fibroids undergoing elective hysterectomy or myomectomy<br>Women between the age of 18-55 with fibroids undergoing elective hysterectomy or myomectomy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Develop an atlas to comprehensively quantify the rate of senescent cell (SnC) types in fibroid and myometrium tissue samples | Perform scRNASeq on human fibroids and control myometrium tissue and apply transfer learning algorithm for SnC identification and phenotyping to identify cell-cell communication patterns in fibroids versus control myometrial tissue using Domino to validate computationally predicted senescent cell types. The computationally predicted immune phenotypes will be validated with flow cytometry. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Validate the concentration senescence-associated secretory profile (SASP) in cell cultures of senescent cells in uterine fibroids | Quantify levels of transcripts and proteins in the fibroid senescence-associated secretory profile (SASP) using ELISA and western blotting techniques | 5 years | 
| Rate of inhibition of cellular proliferation and ECM deposition by senolytics and senomorphics in fibroids | Examine the in-vitro effects of senotherapeutcis using leiomyoma culture models and in mouse models. Measured by inhibition of proliferation, induction of apoptosis, inhibition ECM deposition, decrease in SnCs (senolytics) and senescence-associated secretory profile SASPs (senomorphics). | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Senescent cells, Fibroids, Leiomyomas