Preventive effect of oral mucosal epithelial cell sheets on intrauterine adhesions

Kuramoto, Goro; Takagi, Satoshi; Ishitani, Ken; Shimizu, Tatsuya; Okano, Teruo; Matsui, Hideo

doi:10.1093/humrep/deu326

Cited by 50 publications

(39 citation statements)

References 21 publications

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“…Recent studies have reported increased expression of fibrotic markers, including collagens I and III, in endometrial tissue adhesions (33). Novel therapeutic approaches to treat the disorder, which have been modeled in rodents, but not yet applied in patients, include transplantation of bone marrow‐derived stem cells (34) and oral mucosal cell sheets (35).…”

Section: Discussionmentioning

confidence: 99%

Androgens regulate scarless repair of the endometrial “wound” in a mouse model of menstruation

et al. 2016

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The human endometrium undergoes regular cycles of synchronous tissue shedding (wounding) and repair that occur during menstruation before estrogen-dependent regeneration. Endometrial repair is normally both rapid and scarless. Androgens regulate cutaneous wound healing, but their role in endometrial repair is unknown. We used a murine model of simulated menses; mice were treated with a single dose of the nonaromatizable androgen dihydrotestosterone (DHT; 200 mg/mouse) to coincide with initiation of tissue breakdown. DHT altered the duration of vaginal bleeding and delayed restoration of the luminal epithelium. Analysis of uterine mRNAs 24 h after administration of DHT identified significant changes in metalloproteinases (Mmp3 and -9; P < 0.01), a snail family member (Snai3; P < 0.001), and osteopontin (Spp1; P < 0.001). Chromatin immunoprecipitation analysis identified putative androgen receptor (AR) binding sites in the proximal promoters of Mmp9, Snai3, and Spp1. Striking spatial and temporal changes in immunoexpression of matrix metalloproteinase (MMP) 3/9 and caspase 3 were detected after DHT treatment. These data represent a paradigm shift in our understanding of the role of androgens in endometrial repair and suggest that androgens may have direct impacts on endometrial tissue integrity. These studies provide evidence that the AR is a potential target for drug therapy to treat conditions associated with aberrant endometrial repair processes.-Cousins, F. L., Kirkwood, P. M., Murray, A. A., Collins, F., Gibson, D. A., Saunders, P. T. K. Androgens regulate scarless repair of the endometrial "wound" in a mouse model of menstruation. FASEB J. 30, 2802FASEB J. 30, -2811FASEB J. 30, (2016. www.fasebj.orgIn women, the most important tissues for biosynthesis of androgens are the ovaries, adrenals, and fat. In adult women, 50% of the testosterone measured in blood is secreted by the ovaries and adrenals, with a small midcycle peak (1). The other 50% is derived from conversion of adrenal and ovarian precursors, such as androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate. Testosterone can be further metabolized to both estradiol and the potent nonaromatizable androgen dihydrotestosterone (DHT) in tissues that express aromatase and 5-a reductase enzymes, respectively (1-3).During the menstrual cycle, endometrial breakdown at the time of menses is the culmination of a tightly controlled cascade of biomolecular changes initiated by progesterone (P4) withdrawal (demise of the corpus luteum), which results in shedding of the upper functional layer of the endometrium. Detailed morphologic evaluation in women has revealed that breakdown and restoration of tissue homeostasis at the time of menstruation in normal women occurs rapidly, with epithelialization of the exposed basal stroma completed within 4 d of the first evidence of bleeding (4, 5). Piecemeal degradation and bleeding that give the surface of the endometrium the appearance of a wound has been documented with a hysteroscope intr...

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Section: Discussionmentioning

confidence: 99%

Androgens regulate scarless repair of the endometrial “wound” in a mouse model of menstruation

et al. 2016

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“…Clinical studies using autologous cell sheet‐tissues were performed in the fields of ophthalmology, periodontology, cardiovascular medicine, orthopedics, gastrointestinal surgery, and otolaryngology . Moreover, for treating various diseases, including pneumothorax, diabetes mellitus, hepatic disease, hemophilia, renal dysfunction, endocrinopathy, and uterine disorders, various studies using cell sheet‐tissues are ongoing . In clinical and preclinical studies, OCM will be a powerful tool for evaluating cell sheet‐tissues noninvasively, for example, their thickness, cell condition, and adhesions between layered cell sheets.…”

Section: Discussionmentioning

confidence: 99%

“…[41][42][43][44][45][46] Moreover, for treating various diseases, including pneumothorax, diabetes mellitus, hepatic disease, hemophilia, renal dysfunction, endocrinopathy, and uterine disorders, various studies using cell sheet-tissues are ongoing. [47][48][49][50][51][52][53][54] In clinical and preclinical studies, OCM will be a powerful tool for evaluating cell sheet-tissues noninvasively, for example, their thickness, cell condition, and adhesions between layered cell sheets. Due to its noninvasiveness, it is not necessary to fabricate extra tissues for observation, which results in greater cell savings, lower costs, and less preparation times.…”

Section: Discussionmentioning

confidence: 99%

Optical coherence microscopy of living cells and bioengineered tissue dynamics in high-resolution cross-section

Hasegawa

Haraguchi

Oikaze

et al. 2015

J. Biomed. Mater. Res.

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Optical coherence tomography (OCT) is a valuable tool in the cross-sectional observation/analysis of three-dimensional (3-D) biological tissues, and that histological observation is important clinically. However, the resolution of the technology is approximately 10-20 μm. In this study, optical coherence microscopy (OCM), a tomographic system combining OCT technology with a microscopic technique, was constructed for observing cells individually with a resolution at the submicrometer level. Cells and 3-D tissues fabricated by cell sheet technology were observed by OCM. Importantly, the cell nuclei and cytoplasm could be clearly distinguished, and the time-dependent dynamics of cell-sheet tissues could be observed in detail. Additionally, the 3-D migration of cells in the bioengineered tissue was also detected using OCM and metal-labeled cells. Bovine aortic endothelial cells, but not NIH3T3 murine embryonic skin fibroblasts, actively migrated within the 3-D tissues. This study showed that the OCM system would be a valuable tool in the fields of cell biology, tissue engineering, and regenerative medicine. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 481-488, 2017.

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“…The use of human stem cell treatments for the reconstruction of the endometrium following substantial damage and IUA formation has been hypothesized for some time [96], with studies from animal models showing substantial promise in this area of medical treatment [97–99]. From the first prospective series in humans, 16 women with substantial hysteroscopically confirmed IUAs were treated by uterine intravascular infusions of BMDSC [100].…”

Section: Introductionmentioning

confidence: 99%

“…Ambulatory methods include office hysteroscopy and HSG, with recurrence of more than mild IUAs likely requiring anesthetic and division. Early reintervention with assessment a few weeks after hysteroscopy rather than several months has been suggested in randomized [75] and retrospective studies [99, 100] to both assess and treat recurrence.…”

Section: Introductionmentioning

confidence: 99%

AAGL practice report: practice guidelines on intrauterine adhesions developed in collaboration with the European Society of Gynaecological Endoscopy (ESGE)

Surgery

2017

Gynecol Surg

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Preventive effect of oral mucosal epithelial cell sheets on intrauterine adhesions

Abstract: Transplantation of OMECS offers a reliable method not only to protect the woman's fertility from intrauterine re-adhesion after synechiotomy for IUA or uterine lumen adhesion but also to prevent adhesion after any intrauterine surgery in clinical cases.

Cited by 50 publications

References 21 publications

Androgens regulate scarless repair of the endometrial “wound” in a mouse model of menstruation

Androgens regulate scarless repair of the endometrial “wound” in a mouse model of menstruation

Optical coherence microscopy of living cells and bioengineered tissue dynamics in high-resolution cross-section

AAGL practice report: practice guidelines on intrauterine adhesions developed in collaboration with the European Society of Gynaecological Endoscopy (ESGE)

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