Regeneration in the Primate Uterus: The Role of Stem Cells

Padykula, Helen A.

doi:10.1111/j.1749-6632.1991.tb37849.x

Cited by 168 publications

(116 citation statements)

References 18 publications

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“…This concept is not new and was elegantly described in primate models 38,39 and supported by clonogenicity studies of human derived uterine cells. 16 More recent mouse studies utilizing pulse chase experiments to provide evidence of label retaining cells in the uterus 40,41 provide additional functional evidence to support this idea.…”

Section: Discussionmentioning

confidence: 83%

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

Friel¹,

Sergent²,

Patnaude³

et al. 2008

Cell Cycle

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Recent data suggest that rare stem cell populations with the capacity to self renew and drive tumor formation are a feature of solid tumors. Several investigators have identified putative stem cells from solid tumors and cancer cell lines following isolation of a side population (SP) defined by dye exclusion. We investigated this parameter in our efforts to identify an endometrial cancer (EnCa) stem cell population. Multiple EnCa cell lines were assessed and verapamil sensitive SP and non-SP cells were isolated from two human EnCa cell lines. The functional significance of the SP and non-SP derived from AN3CA was evaluated in vitro and in vivo. SP cells proliferated at a significantly slower rate than the non-SP fraction, and a larger proportion of the SP cells were in the G 1 phase of the cell cycle as compared to the non-SP fraction. The SP fraction was more resistant to the chemotherapeutic agent paclitaxel. The SP comprised ~0.02% of the initial AN3CA cell population and this proportion of SP cells was maintained within the larger heterogeneous population following repeated passages of purified SP cells. These findings suggest that SP cells derived from the AN3CA cell line have the stem cell properties of low proliferative activity, chemoresistance and self-renewal. We also tested relative tumor formation activity of the SP and non-SP fractions. Only the SP fraction was tumorigenic. Additionally, we identified SP fractions in primary EnCa. Together these results are consistent with the hypothesis that EnCa contain a subpopulation of tumor initiating cells with stem like properties.

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Section: Discussionmentioning

confidence: 83%

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

Friel¹,

Sergent²,

Patnaude³

et al. 2008

Cell Cycle

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“…Human endometrium is believed to regenerate from the lower basalis layer, a germinal compartment that persists after menstruation, to give rise to a new functionalis layer (18). The potential of singly dissociated endometrial cells to reconstitute the endometrial tissue raises a possibility that endometrial stem/progenitor cells present in the functionalis layer also may participate in the physiological regeneration of the endometrium through their recycle and reuse.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive and real-time assessment of reconstructed functional human endometrium in NOD/SCID/γ _c ^null immunodeficient mice

Masuda

Maruyama²,

Hiratsu

et al. 2007

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

146

164

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Human uterine endometrium exhibits unique properties of cyclical regeneration and remodeling throughout reproductive life and also is subject to endometriosis through ectopic implantation of retrogradely shed endometrial fragments during menstruation. Here we show that functional endometrium can be regenerated from singly dispersed human endometrial cells transplanted beneath the kidney capsule of NOD/SCID/␥ c null immunodeficient mice. In addition to the endometrium-like structure, hormonedependent changes, including proliferation, differentiation, and tissue breakdown and shedding (menstruation), can be reproduced in the reconstructed endometrium, the blood to which is supplied predominantly by human vessels invading into the mouse kidney parenchyma. Furthermore, the hormone-dependent behavior of the endometrium regenerated from lentivirally engineered endometrial cells expressing a variant luciferase can be assessed noninvasively and quantitatively by in vivo bioluminescence imaging. These results indicate that singly dispersed endometrial cells have potential applications for tissue reconstitution, angiogenesis, and human-mouse chimeric vessel formation, providing implications for mechanisms underlying the physiological endometrial regeneration during the menstrual cycle and the establishment of endometriotic lesions. This animal system can be applied as the unique model of endometriosis or for other various types of neoplastic diseases with the capacity of noninvasive and real-time evaluation of the effect of therapeutic agents and gene targeting when the relevant cells are transplanted beneath the kidney capsule.animal model ͉ bioluminescence imaging ͉ endometriosis ͉ menstruation ͉ angiogenesis H uman endometrium lines the uterus and comprises luminal and glandular epithelial cells, stromal fibroblasts, vascular smooth muscle cells, endothelial cells, and immune competent cells. These cell components coordinately participate in the cyclical changes of human endometrium, including proliferation, differentiation, and tissue breakdown and shedding under the influence of estrogen and progesterone during the menstrual cycle. This unique system of cyclic tissue regeneration also depends on the cyclical growth and regression of the blood vessels that supply the endometrium (1). In addition, angiogenesis is deeply involved in the pathogenesis of endometriumderived disorders such as endometriosis (2). Endometriosis, one of the most common gynecological diseases, is characterized by the presence of functional endometrial-like tissue outside the uterine cavity. It is an estrogen-dependent disorder associated with substantial morbidity; however, the etiology and pathophysiology are not well elucidated (3). To study the physiology of normal endometrium and the pathogenesis of endometriosis, a variety of in vivo models using small animals has been developed by using the transplantation of autologous or heterologous endometrial cells/tissues or endometriotic tissues (4).In the present study, taking advantage of newly de...

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“…To explain this process, it has been proposed that progenitor cells are located in the basal layer of human endometrium (Prianishnikov 1978, Padykula et al 1984, Padykula 1991. The progeny of these cells are rapidly proliferating cells (transient cells) that then move to the functional layer (Padykula et al 1989, Okulicz et al 1997 and actively participate in the regeneration and remodeling of the endometrium.…”

Section: Discussionmentioning

confidence: 99%

Characterization of clonogenic stromal cells isolated from human endometrium

Dimitrov¹,

Timeva²,

Kyurkchiev³

et al. 2008

Reproduction

132

104

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Human endometrium is an object of extensive restructuring and remodeling during the female reproductive life and it is quite tempting to assume that these periodic changes happen with the participation of cells that should have the basic characteristics of multipotent cells. The aim of this study was to search for the presence of cells with plastic adherence, clonogenicity, and differentiation in human endometrium. To this end, human endometrial stromal cells were cultured in vitro for more than 15 passages. Flow cytometry analysis of the cultured cells showed that they were positive for CD29, CD73 and CD90, which are considered to be the markers of cells with mesenchymal origin. The cells were negative for the hematopoietic cell markers (CD45, CD34, CD14, CD3, CD19, CD16/56, and HLA-DR). Further, it was shown that the cultured cells had 15% clonogenic efficiency and could be induced to differentiate into adipogenic cells containing typical lipid-rich vacuoles. These results demonstrate that the human endometrium contains a low number of cells with the characteristics of endometrial stromal stem/progenitor cells, which seem to belong to the family of the mesenchymal stem cells. It can be speculated that these cells are engaged into the monthly restructuring and remodeling of human endometrium.Reproduction (2008) 135 551-558

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Regeneration in the Primate Uterus: The Role of Stem Cells

Cited by 168 publications

References 18 publications

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

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

Noninvasive and real-time assessment of reconstructed functional human endometrium in NOD/SCID/γ _c ^null immunodeficient mice

Characterization of clonogenic stromal cells isolated from human endometrium

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Regeneration in the Primate Uterus: The Role of Stem Cells

Cited by 168 publications

References 18 publications

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

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

Noninvasive and real-time assessment of reconstructed functional human endometrium in NOD/SCID/γ c null immunodeficient mice

Characterization of clonogenic stromal cells isolated from human endometrium

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Noninvasive and real-time assessment of reconstructed functional human endometrium in NOD/SCID/γ _c ^null immunodeficient mice