转化生长因子复合脂肪源性干细胞调控改造盆腔器官脱垂病理微环境的机制和效应研究
发布时间：2019-03-30 17:11
【摘要】：盆腔器官脱垂(POP)是困扰中老年妇女的常见病,目前尚缺乏能够针对病因的治疗方法。现有结果显示POP病人的阴道组织中弹性纤维排列紊乱、含量减少,证实了盆底支持结构破坏可能成为POP的病理因素。我们根据POP临床改变构建并比较了三种动物模型的合理性,结果证实LOXL1(该基因对弹性蛋白的合成和交联起重要作用)敲除老鼠不仅会出现稳定的POP表型,且盆底弹性纤维及胶原合成和排列也出现紊乱,因此认为Loxl1基因敲除老鼠可作为理想的POP动物模型。在找到合理的POP动物模型后,我们制作了 一种丝素微球,复合经TGFβ-1预处理的脂肪来源干细胞来制备可注射丝素-细胞材料,结果显示种植在丝素微球中的ADSCs细胞活性良好,且其LOX家族成员以及弹性蛋白的基因表达量上调。最后将复合ADSC的丝素微球对模型小鼠进行盆底注射,期望增加局部细胞外基质的合成和交联,逆转模型小鼠脱垂表型。本研究期望通过调控干细胞的表达来调控弹性蛋白的合成,并复合组织工程技术手段,为POP的临床治疗提供新思路。
[Abstract]:Pelvic organ prolapse (POP) is a common disease in middle-aged and elderly women. The results showed that the elastic fibers in vaginal tissue of patients with POP were disordered and the content of elastic fibers decreased, which confirmed that the destruction of pelvic floor support structure might be the pathological factor of POP. We constructed and compared the rationality of the three animal models according to the clinical changes of POP. The results showed that LOXL1 (the gene plays an important role in the synthesis and cross-linking of elastin) knockout mice not only showed stable POP phenotypes. Moreover, the synthesis and arrangement of elastic fibers and collagen in pelvic floor were disordered, so it was suggested that Loxl1 knockout mice could be used as an ideal animal model for POP. After finding a reasonable animal model of POP, we made a silk fibroin microspheres combined with adipose-derived stem cells pretreated with TGF 尾-1 to prepare injectable fibroin-cell materials. The results showed that ADSCs cells implanted in silk fibroin microspheres showed good activity, and the expression of LOX family members and elastin genes were up-regulated. Finally, the fibroin microspheres combined with ADSC were injected into the pelvic floor of the model mice in order to increase the synthesis and cross-linking of the local extracellular matrix and reverse the model mice drooping phenotype. The aim of this study is to regulate the synthesis of elastin by regulating the expression of stem cells and to combine tissue engineering techniques to provide a new idea for the clinical treatment of POP.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R711.2
本文编号：2450306
[Abstract]:Pelvic organ prolapse (POP) is a common disease in middle-aged and elderly women. The results showed that the elastic fibers in vaginal tissue of patients with POP were disordered and the content of elastic fibers decreased, which confirmed that the destruction of pelvic floor support structure might be the pathological factor of POP. We constructed and compared the rationality of the three animal models according to the clinical changes of POP. The results showed that LOXL1 (the gene plays an important role in the synthesis and cross-linking of elastin) knockout mice not only showed stable POP phenotypes. Moreover, the synthesis and arrangement of elastic fibers and collagen in pelvic floor were disordered, so it was suggested that Loxl1 knockout mice could be used as an ideal animal model for POP. After finding a reasonable animal model of POP, we made a silk fibroin microspheres combined with adipose-derived stem cells pretreated with TGF 尾-1 to prepare injectable fibroin-cell materials. The results showed that ADSCs cells implanted in silk fibroin microspheres showed good activity, and the expression of LOX family members and elastin genes were up-regulated. Finally, the fibroin microspheres combined with ADSC were injected into the pelvic floor of the model mice in order to increase the synthesis and cross-linking of the local extracellular matrix and reverse the model mice drooping phenotype. The aim of this study is to regulate the synthesis of elastin by regulating the expression of stem cells and to combine tissue engineering techniques to provide a new idea for the clinical treatment of POP.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R711.2
【参考文献】
相关期刊论文 前3条
1 Stuart J Emmerson;Caroline E Gargett;;Endometrial mesenchymal stem cells as a cell based therapy for pelvic organ prolapse[J];World Journal of Stem Cells;2016年05期
2 Wen ZONG;Yan JIANG;Jing ZHAO;Jian ZHANG;Jian-gang GAO;;雌激素对赖氨酰氧化酶(LOX)家族基因表达的影响（英文）[J];Journal of Zhejiang University-Science B(Biomedicine & Biotechnology);2015年10期
3 Yang Zhou;Ouyang Ling;Li Bo;;Expression and significance of lysyl oxidase-like 1 and fibulin-5 in the cardinal ligament tissue of patients with pelvic floor dysfunction[J];Journal of Biomedical Research;2013年01期
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