Stem cells and the reproductive system: Historical perspective and future directions

Duke, Cindy M.; Taylor, Hugh S.

doi:10.1016/j.maturitas.2013.08.012

Cited by 16 publications

(10 citation statements)

References 65 publications

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“…In the wake of these studies, much debate has centered on methodology and interpretation of results . In contrast, the notion that bone marrow cells can transdifferentiate into endometrial lineages has been embraced with a less critical eye and with little reference to relevant debate on bone marrow transdifferentiation in other tissues .…”

Section: Discussionmentioning

confidence: 99%

Bone Marrow Stem Cells Do Not Contribute to Endometrial Cell Lineages in Chimeric Mouse Models

et al. 2017

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Studies from five independent laboratories conclude that bone marrow stem cells transdifferentiate into endometrial stroma, epithelium, and endothelium. We investigated the nature of bone marrow-derived cells in the mouse endometrium by reconstituting irradiated wild type recipients with bone marrow containing transgenic mTert-green fluorescent protein (GFP) or chicken b-actin (Ch b-actin)-GFP reporters. mTert-GFP is a telomerase marker identifying hematopoietic stem cells and subpopulations of epithelial, endothelial, and immune cells in the endometrium. Ch b-actin-GFP is a ubiquitous reporter previously used to identify bone marrowderived cells in the endometrium. Confocal fluorescence microscopy for GFP and markers of endometrial and immune cells were used to characterize bone marrow-derived cells in the endometrium of transplant recipients. No evidence of GFP 1 bone marrow-derived stroma, epithelium, or endothelium was observed in the endometrium of mTert-GFP or Ch b-actin-GFP recipients. All GFP 1 cells detected in the endometrium were immune cells expressing the pan leukocyte marker CD45, including CD3 1 T cells and F4/80 1 macrophages. Further examination of the Ch b-actin-GFP transplant model revealed that bone marrow-derived F4/80 1 macrophages immunostained weakly for CD45. These macrophages were abundant in the stroma, infiltrated the epithelial and vascular compartments, and could easily be mistaken for bone marrow-derived endometrial cells. We conclude that it is unlikely that bone marrow cells are able to transdifferentiate into endometrial stroma, epithelium, and endothelium. This result has important therapeutic implications, as the expectation that bone marrow stem cells contribute directly to endometrial regeneration is shaping strategies designed to regenerate endometrium in Asherman's syndrome and to control aberrant endometrial growth in endometriosis. STEM CELLS 2018;36:91-102 SIGNIFICANCE STATEMENTThe endometrium (the lining of the uterus) is one of the most regenerative tissues in the body, is central to fertility, and is prone to disease. Bone marrow stem cells have been widely reported to transdifferentiate into endometrial cells. This phenomenon was investigated in mouse models, and no evidence of bone marrow cell transdifferentiation into endometrialspecific cell types was found. It was concluded that bone marrow cells are unlikely to transdifferentiate into endometrial cells and that previous reports of this occurring involve the misidentification of immune cells. This result has important implications for the development of therapies to treat diseases of the endometrium.

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Section: Discussionmentioning

confidence: 99%

Bone Marrow Stem Cells Do Not Contribute to Endometrial Cell Lineages in Chimeric Mouse Models

et al. 2017

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“…Several previous researches support that bone marrow stem cells promote endometrial regeneration (Ding et al, 2014;Taylor, 2004;Aghajanova et al, 2010;Duke and Taylor, 2013). In attempting to activate the quiescent endometrium in Asherman's syndrome, ΔNp63+ epithelial cells of endometrium and BMNCs were co-cultured in vitro.…”

Section: Autologous Bone Marrow Mononuclear Cells (Bmncs) Reverse Thementioning

confidence: 94%

Transplantation of collagen scaffold with autologous bone marrow mononuclear cells promotes functional endometrium reconstruction via downregulating ΔNp63 expression in Asherman’s syndrome

Zhao

Cao

Zhu

et al. 2016

Sci. China Life Sci.

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Asherman's syndrome (AS) is a common disease that presents endometrial regeneration disorder. However, little is known about its molecular features of this aregenerative endometrium in AS and how to reconstruct the functioning endometrium for the patients with AS. Here, we report that ΔNp63 is significantly upregulated in residual epithelial cells of the impaired endometrium in AS; the upregulated-ΔNp63 induces endometrial quiescence and alteration of stemness. Importantly, we demonstrate that engrafting high density of autologous bone marrow mononuclear cells (BMNCs) loaded in collagen scaffold onto the uterine lining of patients with AS downregulates ΔNp63 expression, reverses ΔNp63-induced pathological changes, normalizes the stemness alterations and restores endometrial regeneration. Finally, five patients achieved successful pregnancies and live births. Therefore, we conclude that ΔNp63 is a crucial therapeutic target for AS. This novel treatment significantly improves the outcome for the patients with severe AS.Asherman's syndrome, ΔNp63, quiescence, endometrial regeneration, bone marrow stem cell based therapy Citation:

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“…Regarding the therapeutic usefulness, targeting stem cells may be beneficial in accordance with their fundamental role in endometriosis as well as with few seminal, but significant experimental results. Potential usefulness of the SSCs from eutopic endometrium has been already demonstrated in the treatment of several chronic diseases (e.g., diabetes and Parkinson’s disease) ( 54 ). In contrast to these clinical conditions wherein EnSCs may be engaged to provide specific differentiated cells and tissue regeneration, suppression of stem cell recruitment and activity is required in endometriosis.…”

Section: Clinical Perspectivesmentioning

confidence: 99%

Somatic Stem Cells and Their Dysfunction in Endometriosis

Djokovic

Calhaz‐Jorge

2015

Front. Surg.

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Emerging evidence indicates that somatic stem cells (SSCs) of different types prominently contribute to endometrium-associated disorders such as endometriosis. We reviewed the pertinent studies available on PubMed, published in English language until December 2014 and focused on the involvement of SSCs in the pathogenesis of this common gynecological disease. A concise summary of the data obtained from in vitro experiments, animal models, and human tissue analyses provides insights into the SSC dysregulation in endometriotic lesions. In addition, a set of research results is presented supporting that SSC-targeting, in combination with hormonal therapy, may result in improved control of the disease, while a more in-depth characterization of endometriosis SSCs may contribute to the development of early-disease diagnostic tests with increased sensitivity and specificity. Key message: Seemingly essential for the establishment and progression of endometriotic lesions, dysregulated SSCs, and associated molecular alterations hold a promise as potential endometriosis markers and therapeutic targets.

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Stem cells and the reproductive system: Historical perspective and future directions

Cited by 16 publications

References 65 publications

Bone Marrow Stem Cells Do Not Contribute to Endometrial Cell Lineages in Chimeric Mouse Models

Bone Marrow Stem Cells Do Not Contribute to Endometrial Cell Lineages in Chimeric Mouse Models

Transplantation of collagen scaffold with autologous bone marrow mononuclear cells promotes functional endometrium reconstruction via downregulating ΔNp63 expression in Asherman’s syndrome

Somatic Stem Cells and Their Dysfunction in Endometriosis

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