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Endometrial reconstruction from stem cells

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Adult stem cells have been identified in the highly regenerative human endometrium on the basis of their functional attributes. They can reconstruct endometrial tissue in vivo suggesting their possible use in treating disorders associated with inadequate endometrium. The identification of specific markers for endometrial mesenchymal stem cells and candidate markers for epithelial progenitor cells enables the potential use of endometrial stem/progenitor cells in reconstructing endometrial tissue in Asherman syndrome and intrauterine adhesions.

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Endometrial stem/progenitor cells and disorders associated with inadequate endometrium

If endometrial stem/progenitor cells are responsible for regenerating endometrium each menstrual cycle, then their diminished numbers and/or function should result in a thin (<7 mm), dysregulated endometrium, incapable of supporting embryo implantation (9). Similarly, in scarred endometrium or endometrium obliterated with adhesions, functional endometrial stem/progenitor cells likely are lacking, as scant functional endometrium is present in the uterine cavity. In Asherman syndrome there is

Clonogenic Cells

The first evidence for adult stem cells in human endometrium came from cell cloning studies that identified small populations of colony-forming unit (CFU) activity in freshly isolated and purified epithelial (EpCAM+) and stromal (EpCAM) cells (0.22% and 1.25%, respectively) 17, 18. Clones of different sizes were noted for both cell types. The single cell-derived large CFU have self-renewal activity, demonstrated by serial cloning in vitro, and high proliferative potential, undergoing 30–34

Bone marrow-derived stem cells in endometrium

Bone marrow-derived hemopoietic stem cells, MSC, and endothelial progenitor cells circulate in very low numbers, homing to sites of tissue damage. They incorporate into organs, contributing to angiogenesis, or transdifferentiate into the cells of the new tissue in which they reside 42, 43. Circulating myeloid cells also integrate into damaged tissues and transdifferentiate into host tissues, including endometrium 42, 44. Evidence from human and mouse studies suggest that bone marrow-derived

Reconstructing endometrium from endometrial stem/progenitor cells

The substantial evidence indicating that adult stem cell populations exist in human endometrium suggests that it should be possible to activate endogenous endometrial stem/progenitor cells in cases of thin dysfunctional or atrophic endometrium. It should also be possible to transplant endometrial stem/progenitor cells into the uterine cavity in Asherman syndrome or severe cases of IUA as a cell-based therapy for regenerating endometrium. Furthermore, endometrial stem/progenitor cells could be

Generating human endometrium from human embryonic stem cells

Embryonic stem cells are pluripotent stem cells that have potential to differentiate into any cell type in the body. Since isolation of human embryonic stem cells (ESCs) in 1998 (58), much research has focused on directing their differentiation in vitro into clinically relevant cell types for potential use in regenerative medicine (59). A major concern for transplantation of human ESC derivatives into the human body is that the transplanted cell population may include undifferentiated human

Reconstructing other tissues from endometrial and menstrual blood stem/progenitor cells

Bone marrow-derived MSC are an attractive source of cells for regenerative medicine (66). Intravenously infused MSC home to sites of tissue damage, secreting factors that promote tissue repair in a paracrine manner without engraftment (67). These factors are angiogenic, antifibrotic, antiapoptotic, immunosuppressive, and induce mitosis of resident progenitor cells promoting tissue repair (68). The regenerative potential of menstrual blood MSC has been demonstrated in an animal model of Duchenne

Reconstructing endometrium from exogenous cell and organ sources

Innovative approaches have been used to reconstruct endometrial tissue in humans and animal models with the goal of overcoming uterine factor infertility. Recently, autologous bone marrow cells selected by magnetic bead sorting for a mix of fibroblast, MSC and EPCs were instilled into the uterus of a patient with Asherman syndrome and thin dysfunctional endometrium that failed to respond to E (76). The cells were implanted after curettage on day 2 of the patient's menstrual cycle, enabling

Acknowledgment

This article was edited by Carlos Simon.

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      Citation Excerpt :

      Stem cells repair endometrial injury mainly due to their differentiation ability, paracrine activity, and immunomodulatory effects (Fig. 3). It has been reported that transplantation of mesenchymal stem cells (MSCs) or endometrial stem cells into the uterine cavity of IUA patients or female rats can promote endometrial regeneration, which might be due to the potential differentiation ability of stem cells [83]. In addition to direct differentiation into endometrial cells, pluripotent stem cells (PSCs) can also differentiate into other cells such as stromal cells and vascular endothelial cells, which are involved in endometrial repair [84].

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    C.E.G. has nothing to disclose. L.Y. has nothing to disclose.

    Supported by Australian National Health and Medical Research Council grants (545992, 1021126, 1021127) and R.D. Wright Career Development Award 465121 (C.E.G.), Monash IVF Foundation (C.E.G.), the Victorian Government's Operational Infrastructure Support Program and an Australian Postgraduate Award (L.Y.).

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