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间充质干细胞输注患有子宫内膜炎的母马后,所选子宫内膜蛋白表达模式的变化。

Changes in expression pattern of selected endometrial proteins following mesenchymal stem cells infusion in mares with endometrosis.

作者信息

Mambelli Lisley I, Mattos Rodrigo C, Winter Gustavo H Z, Madeiro Dener S, Morais Bruna P, Malschitzky Eduardo, Miglino Maria Angélica, Kerkis Alexandre, Kerkis Irina

机构信息

Laboratório de Genética, Instituto Butantan, São Paulo, SP, Brasil; Programa de Pós-Graduação em Anatomia dos Animais Domésticos e Silvestres da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo, São Paulo, SP, Brasil.

Reprolab, Faculdade de Medicina Veterinária, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil.

出版信息

PLoS One. 2014 Jun 5;9(6):e97889. doi: 10.1371/journal.pone.0097889. eCollection 2014.

Abstract

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 × 10(7)/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.

摘要

间充质干细胞(MSCs)因其自我更新潜力和分化能力而对组织再生有用。MSCs的免疫调节和营养特性已得到证实,这表明它们可作为药物信号细胞,能够积极改变受损组织的局部环境。马子宫内膜异位症是一种进行性退行性疾病,可导致腺体改变和子宫内膜纤维化,从而导致母马不孕。更确切地说,这种疾病的特征是所选子宫内膜蛋白表达模式的表型变化。目前,尚无有效的子宫内膜异位症治疗方法。在此,我们旨在评估同种异体马脂肪组织来源的多能间充质干细胞(eAT-MSCs)输注后这些蛋白的表达模式,并测试这些细胞促进患有子宫内膜异位症母马子宫内膜组织重塑的能力。将eAT-MSC(2×10⁷/只动物)移植到母马子宫内,对照动物仅接受安慰剂。在细胞移植前(第0天)和移植后(第7、21和60天)采集子宫活检样本。在eAT-MSCs移植前后进行了常规组织病理学检查以及层粘连蛋白、波形蛋白、Ki-67抗原、α平滑肌肌动蛋白(α-SMA)和细胞角蛋白18(CK18)等蛋白的表达分析。我们证明,eAT-MSCs通过上述蛋白在细胞内和腺体内定位的变化诱导子宫内膜组织微环境的早期(第7天)重塑。我们证明,eAT-MSCs能够积极调节所研究分泌蛋白的表达模式,并促进腺上皮细胞增殖的诱导,这表明eAT-MSCs移植后对特定子宫内膜组织环境有局部益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a93/4046935/6a70a2c86b08/pone.0097889.g001.jpg

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