Contribution of Bone Marrow-Derived Stem Cells to Endometrium and Endometriosis

Abstract

Bone marrow-derived cells (BMDCs) can differentiate into nonhematopoietic cells, suggesting that BMDCs may contribute to the maintenance of multiple tissues. Donorderived bone marrow cells have been identified in human uterine endometrium. Here, two murine models were used to investigate the contribution of nonendometrial 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 may 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; BMDCs 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. STEM CELLS

Expression Pattern of Stemness-Related Genes in Human Endometrial and Endometriotic Tissues

“…Our preliminary results indicate that the percentages of single cells positive for SALL4 and OCT4 we detected in the stroma of endometriotic tissues are comparable to those found by Gotte M et al for Musashi-1-positive cells (data not shown). The contribution of stem cells to endometriosis has been hypothesized in many reports of studies and reviews (45,14).…”

“…Other studies, also conducted in murine models, demonstrated that stem cells in endometrium derive from bone marrow (14).…”

Characterization of clonogenic stromal cells isolated from human endometrium

“…Another field of study is the potential role of multipotent endometrial stem cells in the pathophysiology of diseases such as endometriosis, endometrial hyperplasia, endometrial cancer, and adenomyosis, which are associated with abnormal endometrial proliferation (Gargett 2004, 2006, Du & Taylor 2007. Alterations in the number, function, regulation, and location of endometrial stem/progenitor cells may be involved in the pathology mechanisms of these endometrial diseases.…”

Functional analyses of the cancer stem cell-like properties of human endometrial tumor initiating cells

“…31 It is not clear, however, whether or not there are multiple classes/gradations of stem/progenitor cells that can give rise to the glandular epithelium and stromal cells. 31,42 In contrast to this concept there are those who have provided evidence to suggest the bone marrow cells can give rise to endometrial cells 30,43 inferring that the bone marrow may harbor a stem cell that has the potential to become an endometrial cell whether it be epithelial or stromal.…”