A novel strategy of mesenchymal stem cells delivery in the uterus of mares with endometrosis

Mambelli, Lisley I.; Winter, Gustavo Henrique Zimmermann; Kerkis, Alexandre; Malschitzky, Eduardo; Mattos, Rodrigo Costa; Kerkis, Irina

doi:10.1016/j.theriogenology.2012.11.030

Cited by 40 publications

(30 citation statements)

References 31 publications

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“…Several lines of experimental evidence suggest that endometrial stem cells function in the development of endometriosis, providing a another mechanism of disease origin . Endometrial stem cells are capable of self‐renewal, multipotency, immunomodulation, homing, and are well positioned to migrate and differentiate under the influence of different stimuli from the surrounding environment . Similarly, we have demonstrated that endometriosis‐derived stem cells retain their potency after leaving the lesion.…”

Section: Discussionsupporting

confidence: 63%

Hematogenous Dissemination of Mesenchymal Stem Cells from Endometriosis

Alderman

Tal

et al. 2018

Stem Cells

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Endometriosis is ectopic growth of endometrial tissue traditionally thought to arise through retrograde menstruation. We aimed to determine if cells derived from endometriosis could enter vascular circulation and lead to hematogenous dissemination. Experimental endometriosis was established by transplanting endometrial tissue from DsRed+ mice into the peritoneal cavity of DsRed- mice. Using flow cytometry, we identified DsRed+ cells in blood of animals with endometriosis. The circulating donor cells expressed CXCR4 and mesenchymal stem cell (MSC) biomarkers, but not hematopoietic stem cell markers. Nearly all the circulating endometrial stem cells originated from endometriosis rather than from the uterus. Cells expressing DsRed, CXCR4, and MSCs markers were identified in the peritoneal wall and surrounding vessels of recipient mice, contributing to both endometriosis and angiogenesis. Cells originating in endometriosis lesions migrated and implanted in lung tissue and displayed makers of differentiation, indicating retained multipotency. In vitro these cells demonstrated multipotency and were able to differentiate into adipogenic, osteogenic, and chondrogenic lineages. Endometriosis lesions also expressed high levels of CXCL12, the CXCR4 receptor ligand. Serum CXCL12 levels were greater than in sham control mice. In humans with endometriosis, serum CXCL12 levels were significantly higher than controls, suggesting that the CXCL12/CXCR4 axis is operational in women with spontaneous endometriosis as well. Stem cells, rather than differentiated cells from endometriosis, enter the circulation in response to CXCL12. We identify an endometriosis-derived stem cell population, a potential mechanism of dissemination of this disease and a potential target for treatment of endometriosis. Stem Cells 2018;36:881-890.

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Section: Discussionsupporting

confidence: 63%

Hematogenous Dissemination of Mesenchymal Stem Cells from Endometriosis

Alderman

Tal

et al. 2018

Stem Cells

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“…The procedure of eAT-MSCs infusion was performed during synchronized estrus according as previously reported [19]. After cleaning the perineal area, the operator wearing a sterile insemination glove, introduced a disposable insemination pipette through the cervix to the uterus body.…”

Section: Methodsmentioning

confidence: 99%

Changes in Expression Pattern of Selected Endometrial Proteins following Mesenchymal Stem Cells Infusion in Mares with Endometrosis

et al. 2014

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Mesenchymal stem cells (MSCs) due to their self-renewal potential and differentiation capacity are useful for tissue regeneration. Immunomodulatory and trophic properties of MSCs were demonstrated suggesting their use as medicinal signaling cells able to positively change local environment in injured tissue. Equine endometrosis is a progressive degenerative disease responsible for glandular alterations and endometrial fibrosis which causes infertility in mares. More precisely, this disease is characterized by phenotypic changes in the expression pattern of selected endometrial proteins. Currently, no effective treatment is available for endometrosis. Herein, we aimed at the evaluation of expression pattern of these proteins after allogeneic equine adipose tissue-derived multipotent mesenchymal stem cells (eAT-MSCs) infusion as well as at testing the capacity of these cells to promote endometrial tissue remodeling in mares with endometrosis. eAT-MSC (2×107/animal) were transplanted into mares’ uterus and control animals received only placebo. Uterine biopsies were collected before (day 0) and after (days 7, 21 and 60) cells transplantation. Conventional histopathology as well as expression analysis of such proteins as laminin, vimentin, Ki-67-antigen, α-smooth muscle actin (α-SMA) and cytokeratin 18 (CK18) have been performed before and after eAT-MSCs transplantation. We demonstrated that eAT-MSCs induced early (at day 7) remodeling of endometrial tissue microenvironment through changes observed in intra cellular and intra glandular localization of aforementioned proteins. We demonstrated that eAT-MSCs were able to positively modulate the expression pattern of studied secretory proteins as well as, to promote the induction of glandular epithelial cells proliferation suggesting local benefits to committed endometrial tissue environment after eAT-MSCs transplantation.

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“…Another evolving treatment for endometritis and endometrial degeneration is the use of stem cells, and researchers are investigating stem cells as a potential treatment for uterine degeneration. Post breeding uterine inflammation was altered after treatment with stem cells , and stem cells were shown to successfully migrate into the endometrium in mares with degenerative changes, thus there is the potential for the cells to improve uterine quality . As with the PRP research, more information is needed to determine the prospective use of stem cells as a treatment in clinical cases.…”

Section: Treatmentsmentioning

confidence: 99%

Inflammatory mechanisms of endometritis

Woodward

Troedsson

2015

Equine Veterinary Journal

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Transient post breeding endometritis is a normal physiological reaction in the mare, as it is believed that an inflammatory response is necessary for the effective removal of contaminating bacteria and excess spermatozoa introduced into the uterus. While most mares can clear endometritis within a reasonable amount of time, persistent endometritis caused by either bacteria or spermatozoa can threaten the success of a pregnancy. A subpopulation of mares is susceptible to persistent endometritis, and these mares are a concern in equine reproductive medicine. Research has identified several factors that contribute to susceptibility; however, the exact mechanisms of the progression of the disease are still being elucidated. Current research focuses on endometrial gene expression during endometritis in an attempt to understand the timing of specific inflammatory processes involved with the development of susceptibility to persistent endometritis. With an increased understanding of the mechanisms involved with the disease, current treatments can be improved upon, and new treatments can be developed to target affected pathways.

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A novel strategy of mesenchymal stem cells delivery in the uterus of mares with endometrosis

Cited by 40 publications

References 31 publications

Hematogenous Dissemination of Mesenchymal Stem Cells from Endometriosis

Hematogenous Dissemination of Mesenchymal Stem Cells from Endometriosis

Changes in Expression Pattern of Selected Endometrial Proteins following Mesenchymal Stem Cells Infusion in Mares with Endometrosis

Inflammatory mechanisms of endometritis

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