Contribution of Bone Marrow Derived Stem Cells to Endometrium and Endometriosis

¹ Division of Reproductive Endocrinology and Department of Molecular, Cellular and Developmental Biology, Yale University, 333 Cedar Street, New Haven, CT 06520

	Abstract

Bone marrow-derived cells (BMDCs) can differentiate into nonhematopoietic cells, suggesting that BMDCs may contribute to the maintenance of multiple tissues. Donor-derived bone marrow cells have been identified in human uterine endometrium. Here two murine models were used to investigate the contribution of non-endometrial stem cells to endometrium. We investigate whether BMDCs can localize to uterine endometrium and to endometriosis. After bone marrow transplantation, male donor-derived bone marrow cells were found in the uterine endometrium of female mice. Although uncommon (<0.01%), these cells can differentiate into epithelial cells. After generation of experimental endometriosis by ectopic endometrial implantation in the peritoneal cavity, bone marrow from LacZ transgenic mice was used for transplantation. LacZ expressing cells were found in the wild type ectopic endometrium implanted in the peritoneal cavity of hysterectomized LacZ transgenic mice. The repopulation of endometrium with bone marrow derived stem cells may be important to normal endometrial physiology, and also help to explain the cellular basis for the high long-term failure of conservative alternatives to hysterectomy. The examination of a sexually dimorphic organ such as the uterus demonstrates the ability of male bone marrow, which cannot harbor circulating endometrial cells, to generate endometrium de novo and proves their mesenchymal stem cell origin. Finding Y chromosome bearing endometrial cells demonstrates the potential to recapitulate embryonic developmental pathways that were never activated in males; BMDC may have vast regenerative capacity. Additionally the ability of stem cells to engraft endometriosis has implications for the origin and progression of this disease. Ectopic differentiation of stem cells may be a novel mechanism of disease.

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