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Endometriosis Cell Proliferation Induced by Bone Marrow Mesenchymal Stem Cells

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Abstract

Endometriosis is an estrogen-dependent gynecological disorder that affects 10% of reproductive-aged women and causes pelvic pain and infertility. Bone marrow–derived stem cells (BMDCs) are known to engraft endometriosis in association with lesion growth; however, they do not undergo significant clonal expansion. The indirect effects of BMDCs on endometriosis growth and cell proliferation are not well characterized. Here, we demonstrate that BMDCs’ co-culture increased endometrial stromal cell proliferation. In vitro studies using endometrial cells showed that BMDCs increased cell proliferation and activation of CDK1 in both an endometriosis cell line and primary endometrial stromal cells from women with endometriosis, however not in normal endometrial cells. In vivo studies using a mouse model of endometriosis showed increased CDK1+ expression associated with engrafted GFP + BMDCs. These results suggest that endometrial cell proliferation is induced by stem cell–derived trophic factors leading to the growth of endometriotic lesions. Targeting the specific signaling molecules secreted by BMDC may lead to novel therapeutic strategies for controlling cell proliferation in endometriosis.

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Funding

This work was supported by the Endometriosis Foundation of America AWD0003567.

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Author notes

  1. Peng Chen

    Present address: Obstetrics and Gynecology Department, Shengjing Hospital of China Medical University, Shenyang, 110004, Liaoning, China

  2. Peng Chen and Ramanaiah Mamillapalli contributed equally to this work.

Authors and Affiliations

  1. Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA

    Peng Chen, Ramanaiah Mamillapalli, Shutaro Habata & Hugh S. Taylor

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  1. Peng Chen
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Correspondence to Ramanaiah Mamillapalli.

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ESM 1

Gross morphology of endometriotic lesions: Circles (white) indicate endometriotic lesions (left). H & E staining of lesion tissue section showing glandular uterine structure (right).(DOCX 11.7 kb)

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Chen, P., Mamillapalli, R., Habata, S. et al. Endometriosis Cell Proliferation Induced by Bone Marrow Mesenchymal Stem Cells. Reprod. Sci. 28, 426–434 (2021). https://doi.org/10.1007/s43032-020-00294-4

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  • DOI: https://doi.org/10.1007/s43032-020-00294-4

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