Characterization of clonogenic stromal cells isolated from human endometrium

Dimitrov, Roumen; Timeva, Tanya; Kyurkchiev, Dobroslav; Stamenova, Maria; Shterev, A; Kostova, P; Zlatkov, Viktor Yordanov; Kehayov, И.; Kyurkchiev, Stanimir

doi:10.1530/rep-07-0428

Cited by 131 publications

(114 citation statements)

References 35 publications

(41 reference statements)

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“…Mesenchymal stem cells found in the stroma and epithelial progenitor cells are thought to drive this dynamic regenerative capacity of the endometrium (17,18). Unlike the epithelial progenitor cells that appear to be locked into an epithelial cell fate, mesenchymal stem cells can give rise to diverse cell types such as smooth muscle cells, adipocytes, chondrocytes, and osteoblasts (18).…”

Section: Resultsmentioning

confidence: 99%

High-grade serous ovarian cancer arises from fallopian tube in a mouse model

Kim

Coffey²,

Creighton

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

348

317

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Although ovarian cancer is the most lethal gynecologic malignancy in women, little is known about how the cancer initiates and metastasizes. In the last decade, new evidence has challenged the dogma that the ovary is the main source of this cancer. The fallopian tube has been proposed instead as the primary origin of high-grade serous ovarian cancer, the subtype causing 70% of ovarian cancer deaths. By conditionally deleting Dicer, an essential gene for microRNA synthesis, and Pten, a key negative regulator of the PI3K pathway, we show that high-grade serous carcinomas arise from the fallopian tube in mice. In these Dicer-Pten doubleknockout mice, primary fallopian tube tumors spread to engulf the ovary and then aggressively metastasize throughout the abdominal cavity, causing ascites and killing 100% of the mice by 13 mo. Besides the clinical resemblance to human serous cancers, these fallopian tube cancers highly express genes that are known to be up-regulated in human serous ovarian cancers, also demonstrating molecular similarities. Although ovariectomized mice continue to develop high-grade serous cancers, removal of the fallopian tube at an early age prevents cancer formation-confirming the fallopian tube origin of the cancer. Intriguingly, the primary carcinomas are first observed in the stroma of the fallopian tube, suggesting that these epithelial cancers have a mesenchymal origin. Thus, this mouse model demonstrates a paradigm for the origin and initiation of high-grade serous ovarian carcinomas, the most common and deadliest ovarian cancer.epithelial ovarian cancer | oviduct | mesenchymal-to-epithelial transition | carcinoma initiation E pithelial ovarian cancer, accounting for 90% of all ovarian tumors, is grouped into four major histologic types: serous (70%), endometrioid (10-15%), clear-cell (10%), and mucinous (3%) carcinomas (1). The serous-type cancers are also overwhelmingly high-grade (90%)-the culprit of 70% of ovariancancer deaths and a key contributor to an overall ovarian cancer 5-yr survival rate of 31% (2-4). Most cases of high-grade serous ovarian cancers are diagnosed at advanced stages, when the tumors have already metastasized. Despite the steady improvement of surgery and chemotherapy, >90% of women with advanced ovarian cancers die after the cancer relapses (5). Early detection of these high-grade serous carcinomas is thus key to reducing ovarian cancer deaths (6). However, the origin and molecular pathogenesis of these high-grade serous ovarian cancers are largely unknown (1, 6).Despite widespread peritoneal metastasis commonly seen in ovarian cancer at diagnosis, the ovary has long been considered the primary origin of this cancer-hence the name ovarian cancer. However, precursor lesions have not been identified in the ovary (1, 7). Over the past decade, new evidence has emerged to propose a different source of ovarian cancer: the fallopian tube (7,8). After women with hereditary breast and ovarian cancer-susceptibility gene (BRCA1, BRCA2) mutations have their ovaries and fallop...

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Section: Resultsmentioning

confidence: 99%

High-grade serous ovarian cancer arises from fallopian tube in a mouse model

Kim

Coffey²,

Creighton

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

348

317

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“…Stromal cells have been shown to be quiescent in vivo. It is only after their isolation and culturing in vitro for 15 passages that clonogenic endomerial stromal cells differentiate into fibroblastlike elongated cells forming a monolayer (Dimitrov et al 2008). However, these cells were shown to be stimulated in vivo when tissue is damaged (Ramalho-Santos et al 2002, Venezia et al 2004, suggesting that endometrial regeneration may be the result of the tissue breakdown caused during menses.…”

Section: Inflammation-induced Regeneration Of Endometrial Tissuementioning

confidence: 99%

Endometrial inflammation and effect on implantation improvement and pregnancy outcome

2012

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Implantation failure, which is presently the major barrier in human fertility, is attributed, in many cases, to the failure of the uterus to acquire receptivity. The transition into a receptive uterus includes cellular changes in the endometrium and the modulated expression of different cytokines, growth factors, transcription factors, and prostaglandins. These molecules partake in the generation of an inflammatory response followed by the recruitment of immune cells. These cells have shown to be involved in the maternal immune tolerance toward the implanted embryo as well as in the maternal-fetus interaction during pregnancy. Most of the accumulated evidence indicates that embryo implantation is associated with an active Th1 inflammatory response while a Th2-humoral inflammation is required for pregnancy maintenance. Yet, recent findings suggest that a Th1 inflammatory response is also necessary for the acquisition of uterine receptivity. This notion was originally suggested by reports from our and other clinical centers worldwide that IVF patients with repeated implantation failure subjected to endometrial biopsy exhibit a substantial improvement in their chances to conceive. These findings, followed by the demonstration of an elevated pro-inflammatory cytokine/chemokine expression, as well as an increased abundance of immune cells, in the endometrium of these patients, raised the idea that acquisition of uterine receptivity is closely associated with an inflammatory response. This review summarizes the molecular and biochemical evidence that confirm this notion and proposes a mechanism by which injury-induced inflammation improves uterine receptivity and the subsequent pregnancy outcome.Reproduction (2012) 144 661-668

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“…Indeed, we successfully isolated endometrial SP (ESP) cells from SDECs (Masuda et al 2005(Masuda et al , 2008(Masuda et al , 2010. Other laboratories have identified candidate endometrial stem/progenitor cells, including clonogenic endometrial cells (Chan et al 2004), ESP cells (Kato et al 2007, Tsuji et al 2008 (Dimitrov et al 2008) and some other populations (Meng et al 2007, Musina et al 2008. Only in vitro functional properties of these cells, however, have been investigated.…”

Section: Stem/progenitor Cells In Human Endometriummentioning

confidence: 99%

Human uterine stem/progenitor cells: their possible role in uterine physiology and pathology

Maruyama¹,

Masuda²,

Ono³

et al. 2010

Reproduction

100

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The human uterus mainly consists of the endometrium and the outer smooth muscle layer termed the myometrium. The uterus harbours the exceptional and remarkable regenerative ability responsible for cyclical regeneration and remodelling throughout the reproductive life. The uterus must swiftly and cooperatively enlarge to hold the growing foetus during pregnancy. Furthermore, the endometrium, in particular the functionalis layer, must also regenerate, differentiate and regress with each menstrual cycle under hormonal control. Endometrial regeneration from the basal layer is thought to contribute to replacement of the functionalis layer followed by its slough off during menses and parturition. These morphological and functional features of human endometrium can be reproduced in murine models in which severely immunodeficient mice are xenotransplanted with dispersed human endometrial cells under the kidney capsule. The uterine myometrium possesses the similar plasticity of the endometrium. This is demonstrated by multiple cycles of pregnancyinduced enlargement and regression after parturition. It is likely that regeneration and remodelling in the female reproductive tract are achieved presumably through endometrial and myometrial stem cell systems. Recent evidence now supports the existence of these stem cell systems in humans. Here, we will review our current understanding of uterine stem/progenitor cells. We also propose a novel hypothetical model in which stem cell activities explain the physiological remodelling and regeneration of the human uterus and the pathogenesis of gynaecological diseases such as endometriosis.

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Characterization of clonogenic stromal cells isolated from human endometrium

Cited by 131 publications

References 35 publications

High-grade serous ovarian cancer arises from fallopian tube in a mouse model

High-grade serous ovarian cancer arises from fallopian tube in a mouse model

Endometrial inflammation and effect on implantation improvement and pregnancy outcome

Human uterine stem/progenitor cells: their possible role in uterine physiology and pathology

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