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.
Zusammenfassung: Cyclosporin A ist ein potenter immunsuppressiver Wirkstoff, der in der Therapie der Equinen rezidivierenden Uveitis (ERU) in Form eines suprachoroidalen CsA-Implantats eingesetzt wird, mit dem hohe CsA-Konzentrationen im Glaskörper erreicht werden kön-nen. Dies soll insbesondere bei Appaloosas, die eine besondere Form der Uveitis aufweisen, wirkungsvoll sein. Ziel dieser Arbeit war es, die Besonderheiten der Uveitis bei Appaloosas, Knabstruppern und anderen Tigerschecken herauszufinden und damit herauszustellen, ob eine Vitrektomie oder ein CsA-Implantat zu deren Therapie sinnvoller ist. Dazu wurden die Daten von 2263 Pferden mit Uveitis nach den Punkten Alter, betroffene Augen, Leptospirenbefund, Verlaufsform der Uveitis, Augenuntersuchungsbefund und Sehfähigkeit ausgewertet. Sowohl bei Appaloosas und Knabstruppern, als auch beim Farbschlag der Tigerschecken konnten mehrere Besonderheiten der Uveitis herausgearbeitet werden. Diese Rassen bzw. dieser Farbschlag werden erst in einem überdurchschnittlichen Alter von 11,1 bis 12,2 Jahren zur Untersuchung vorgestellt (p < 0,001), was vor allem darauf zurückzuführen ist, dass sie signifikant häufiger an der schleichenden Verlaufsform der Uveitis erkranken (p < 0,0001), die ohne schmerzhafte Entzündungsschübe einhergeht und daher oft erst spät bemerkt wird. Aufgrund des schleichenden Verlaufs können bei diesen in der Augenuntersuchung häufiger Befunde festgestellt werden, die auf eine chronische Erkrankung hinweisen, wie hintere Synechien, Linsen(sub)luxationen, diffuse Katarakte oder eine Atrophia / Phthisis bulbi. Auch der Anteil bereits ein-oder beidseitig erblindeter Pferde ist bei diesen Rassen bzw. diesem Farbschlag mit je über 60 % signifikant höher (p < 0,0001) als bei Pferden anderer Rasse oder Farbe. Bei Pferden mit schleichender Uveitis können außerdem seltener Leptospiren im Auge als Ursache für die Uveitis gefunden werden (p < 0,0001). Insbesondere Appaloosas, Knabstrupper bzw. Tigerschecken leiden signifikant seltener an einer leptospirenbedingten Uveitis (p < 0,0001) als Pferde anderer Rassen und Farbe. Der Anteil negativer Befunde liegt bei diesen bei über 55 %, im Gegensatz zu 16% bei anderen Pferden. Eine weitere Besonderheit der Uveitis dieser Rassen bzw. dieser Farbe ist das gehäuft beidseitige Auftreten der Erkrankung (p< 0,0001). Aufgrund der Tatsache, dass Leptospiren bei der Uveitis der Appaloosas, Knabstrupper bzw. Tigerschecken seltener eine Rolle spielen, ist die Vitrektomie zur Entfernung von Glaskörpertrübungen, nicht aber zur Verhinderung weiterer Entzündungsschübe geeignet. Ein suprachoroidales CsA-Implantat mit kontinuierlicher Abgabe von CsA in die Augengewebe und -flüssigkeiten könnte allerdings gerade bei Pferden mit schleichender Verlaufsform von Vorteil sein, um die chronische Entzündung zu kontrollieren, da aufgrund der fehlenden, äußeren Symptome eine konservative Therapie nicht durchführbar ist. Daher wäre eine Zulassung dieses Implantats dringend nötig, um eine optimale Versorgung der Pferde mit negativem Lepto...
The use of butafosfan in combination with cobalamin modulates many cellular metabolic functions in several species. Its use enhances productive and reproductive performance and reduces stress responses in animals. Despite all these attributes, so far there have been no controlled studies to evaluate the effects of butafosfan and cobalamin on the quality of stallion semen. The purpose of this study was to evaluate the action of butafosfan in combination with cobalamin on the quality of fresh and cooled stallion semen. Four healthy stallions were kept in the same place and under the same management conditions during the entire experiment. Stallions were randomly assigned to two treatment groups in a 2x2 crossover design. Group A stallions were treated with an intramuscular injection of butafosfan twice a week for 80 days, while group B did not receive any treatment. After that, both groups were not treated for another 80 days allowing a washout period for the treated group. Then, the groups were reversed, and group B was treated with butafosfan and group A acted as the control for another 80 days. Semen was collected twice a week, diluted in skim milk and evaluated for total sperm count, total and progressive sperm motility, membrane integrity (CFDA/PI staining) and membrane functionality (HOS test) at 0 and 24 hours after preservation at 5ºC. Data were analyzed by comparing the values obtained from the treated stallions between the 60 th and 84 th days of treatment and the values obtained from the same stallion during the control period. The ejaculates of the washout period and between days 1 and 63 of treatment were not considered. A total of 85 ejaculates were analyzed by one-way ANOVA. Means were compared by the Tukey test at the 5% level of significance. No significant differences were observed in fresh and cooled semen regarding the total sperm count, total motility, progressive motility, membrane integrity and membrane functionality in the treated and control groups respectively. No interactions were detected in the fresh and cooled semen. The use of butafosfan and cobalamin in the stallions did not affect the seminal quality of young and fertile stallions. It can be used routinely and safely in these stallions. However, contrary to observations in humans and in bulls, the use of cobalamin did not improve semen parameters in these stallions. ResumoA utilização de Butafosfan em combinação com cobalamina modula uma série de funções metabólicas celulares em várias espécies. Seu uso melhora o desempenho produtivo e reprodutivo e reduz as respostas ao estresse em animais. Apesar de todos esses atributos, até agora não houve estudos controlados para avaliar os efeitos da substância Butafosfan e cobalamina sobre a qualidade do sêmen de garanhões. O objetivo deste estudo foi avaliar a ação do Butafosfan em combinação com cobalamina sobre a qualidade do sêmen fresco e resfriado de garanhões. Quatro garanhões saudáveis foram mantidos no mesmo lugar e sob as mesmas condições de manejo durante todo o experimen...
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