CXCR4 or CXCR7 antagonists treat endometriosis by reducing bone marrow cell trafficking

Nicola Pluchino, Ramanaiah Mamillapalli, Shafiq Shaikh, Shutaro Habata, Aya Tal, Marie Gaye, Hugh S Taylor
Journal of cellular and molecular medicine · 2020 · vol. 24(4) , pp. 2464–2474 · doi:10.1111/jcmm.14933 · PMID:31904910 · W2998725929
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Abstract

Adult stem cells have a major role in endometrial physiology, including remodelling and repair. However, they also have a critical role in the development and progression of endometriosis. Bone marrow-derived stem cells engraft eutopic endometrium and endometriotic lesions, differentiating to both stromal and epithelial cell fates. Using a mouse bone marrow transplantation model, we show that bone marrow-derived cells engrafting endometriosis express CXCR4 and CXCR7. Targeting either receptor by the administration of small molecule receptor antagonists AMD3100 or CCX771, respectively, reduced BM-derived stem cell recruitment into endometriosis implants. Endometriosis lesion size was decreased compared to vehicle controls after treatment with each antagonist in both an early growth and established lesion treatment model. Endometriosis lesion size was not effected when the local effects of CXCL12 were abrogated using uterine-specific CXCL12 null mice, suggesting an effect primarily on bone marrow cell migration rather than a direct endometrial effect. Antagonist treatment also decreased hallmarks of endometriosis physiopathology such as pro-inflammatory cytokine production and vascularization. CXCR4 and CXCR7 antagonists are potential novel, non-hormonal therapies for endometriosis.

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mesh:D004715endometriosis

MeSH descriptors

Benzylamines Bone Marrow Cells Cell Movement Cyclams Endometriosis Endometrium Receptors, CXCR Receptors, CXCR4 Adult Stem Cells Adult Stem Cells Adult Stem Cells Animals Benzylamines Bone Marrow Cells Bone Marrow Cells Bone Marrow Transplantation Bone Marrow Transplantation Cell Movement Cyclams Endometriosis

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