尿路上皮分化有关的特异糖蛋白Uroplakin

人类尿路上皮和其它哺乳类动物一样 ,均由复层移行上皮覆盖着整个泌尿道 ,包括肾盏、肾盂、输尿管、膀胱和尿道。这种上皮有许多特点 :(1)生物学行为的多变性。移行上皮是哺乳动物中少见的出生后可以“转分化”为其它上皮类型的实例之一。它可以在某些特定的间质影响下分化为前列腺上皮 ,也可以在某些未知条件下化生为鳞状上皮、腺上皮等 ,出现了临床上的膀胱白斑、膀胱鳞状细胞癌、腺性和囊性膀胱炎、膀胱腺癌、尿路移行细胞癌等一些与分化相关的疾病。 (2 )可以诱导异位的骨形成。(3)近些年发现有一组与尿路上皮分化相关的尿路上皮特异性…     

移行上皮特异标志物Uroplakins在膀胱疾病中的意义

在泌尿系统疾病中膀胱疾病非常多见,如感染、肿瘤等,这些疾病主要发生在膀胱移行上皮。长期以来,寻找移行上皮特异的标志物在膀胱疾病的诊断和治疗中具有重要意义。本文简单介绍了膀胱移行上皮细胞分化的标志物uroplakins的生物学特征,并阐述了其在膀胱疾病的诊断和治疗中的作用。     

移行上皮特异标志物Uroplakins在膀胱疾病中的意义

在泌尿系统疾病中膀胱疾病非常多见，如感染、肿瘤等，这些疾病主要发生在膀胱移行上皮。长期以来，寻找移行上皮特异的标志物在膀胱疾病的诊断和治疗中具有重要意义。本文简单介绍了膀胱移行上皮细胞分化的标志物Uroplakins的生物学特征，并阐述了其在膀胱疾病的诊断和治疗中的作用。     

尿路上皮性肿瘤的诊断

整个尿路从肾盏、肾盂、输尿管、膀胱及前列腺尿道均为移行性上皮所覆盖，移行性上皮细胞发生的肿瘤谓之尿路上皮肿瘤。尿路上皮肿瘤可为多发性，一处发现了肿瘤，应注意全尿路的检查，如膀胱发现了肿瘤，应注意上尿路及前列腺尿道的检查，以免发生遗漏。尿路上皮肿瘤以膀...     

肾结核并双侧全程尿路移行细胞癌1例

移行细胞癌是泌尿系统肿瘤常见的病理类型,其中膀胱上皮移行细胞癌约占90%～95%,上尿路移行细胞癌（肾盂癌、输尿管癌）约占5%。双侧上尿路、膀胱全程出现移行细胞癌则较为少见,而肾结核同时合并双侧全程尿路移行细胞癌则更是罕见报道。我院于2011年收治1例,报告如下。     

膀胱尿路上皮肿瘤的病理

“尿路上皮”(urothelium)一词首先由Melicow于1945年使用。应用这一名称是基于肾盏、肾盂、输尿管、膀胱及前列腺部尿道皆被覆移行上皮细胞,各段的移行上皮胚胎学来源相同,细胞形态、组织学结构相同,各段的功能皆为引流尿液,尿液通过时移行上皮没有什么改变,还有各段移行上皮的良恶性肿瘤的组织病理学和生物学行为基本相同。于是将这一系统的移行上皮总称为尿路上皮。     

尿路上皮分化特异糖蛋白与膀胱癌分化的相关性研究

探讨尿路上皮分化特异的糖蛋白表达与膀胱癌分化程度的相关性。方法用免疫组织化学方法研究ＵＰⅡ－Ⅲ在９６例膀胱移行细胞癌的表达情况,并与膀胱癌的ＷＨＯ分进行对照研究。结果ＵＰ在Ｇ１组乳头状移行细胞癌的表达率为１００．０％,Ｇ２组为９０．５％,两组差异无显著。     

盐酸米托蒽醌膀胱灌注预防尿路上皮移行细胞癌复发

目的：评价盐酸米托蒽醌膀胱灌注预防尿路移行上皮细胞癌膀胱内复发的有效性、患者耐受性及其毒副作用。方法：对21例手术后经病理检查证实为尿路上皮移行细胞癌而且保留膀胱的患者，以盐酸米托蒽醌作膀胱灌注，记录膀胱灌注过程中的相关情况。结果：随访1～12个月，4例复发，1例恶化，复发率为19．0％(4／21)，1年未复发率76．2％(16／21)，平均无瘤间期10．3个月。9例发生局部并发症，复查血常规及肝、肾功能灌注前后差异无统计学意义。结论：初步随访证实，盐酸米托蒽醌降低尿路上皮移行细胞癌术后复发，大部分患者耐受良好，无明显全身毒副作用。     

膀胱低恶倾向乳头状尿路上皮肿瘤的临床与病理

目的：探讨膀胱低恶倾向乳头状尿路上皮肿瘤(PUNLMP)病理特点及临床治疗措施。方法：21例石蜡包埋标本源于膀胱镜活检16例，经尿道膀胱肿瘤切除术(TURBT)5例。患者男11例，女10例。平均年龄57岁。其中伴血尿14例，下尿路刺激症状4例，下尿路不全梗阻2例，偶然发现1例。病理切片符合1998年WHO／ISUP PUNLMP病理诊断标准。同期尿路上皮乳头状瘤3例，Ⅰ级乳头状移行细胞癌11例，Ⅱ～Ⅲ级乳头状移行细胞癌38例作为对照。结果：21例患者行TURBT19例，膀胱部分切除术2例。病理检查：PUNLMP乳头的尿路上皮细胞排列规则，细胞核可有轻度不典型增生，尿路上皮可轻度增厚，层次可超过7层，细胞核分裂相少见且仅在基底层，没有浸润和转移。平均随访12个月，复发1例。结论：膀胱低恶倾向乳头状尿路上皮肿瘤具有独立的病理特点，以局部治疗为主，需长期随诊。     

尿路上皮多器官癌

１９７５～１９９２年底在本院手术治疗病理证实的尿路上皮癌４１３例（肾盂移行上皮癌３４例；输尿管移行上皮癌１９例；胱移行上皮癌３５１例；尿道移行上皮癌９例）。如果以尿道肿瘤为１，各部位发生尿路上皮肿瘤机会之比为：肾盂：输尿管：膀胱：尿道＝３．７８：２．１１：３９：１。其中２２例属尿路上皮多器官癌。各部位发生多器官肿瘤的机会：肾盂１３／３４（３８．２３％），输尿管１４／１９（７３．６８％），膀胱１６／３５１（４．５６％），尿道４／９（４４．４４％）。非同时发生的肿瘤间期５～６２个月。其中一例尿路上皮癌者三年前患结肠癌。     

Bioartifizielles autologes Urothel etabliert aus Spülungen der Harnblase

Reconstructive surgery of lower urinary tract disorders can be limited by a shortage of adequate autologous tissue. Tissue engineering is an option for surgical reconstruction with evolved biological substitutes. Urethral repair with bioartificial urothelial implants can be an innovative method for sustained urothelial regeneration in situ. The needed urothelial cells are commonly isolated from native urothelium requiring surgery.The aim of this study was to establish primary human urothelial cell cultures from bladder washings in serum-free media and to generate urothelial tissue without seeding of matrices in a feeder cell-free system. It could be demonstrated that under these conditions bioartificial urothelium can be developed successfully from bladder washings. Its multilayered cellular structure and the initial differentiation in vitro, similar to native-grown urothelial tissue, are promising with regard to intended clinical application. Current work focuses on establishing cell culture techniques according to legal regulations, terminal differentiation of the urothelial constructs in vitro, and techniques to surgically implant lab-grown bioartificial urothelium.     

Amniotic fluid and bone marrow derived mesenchymal stem cells can be converted to smooth muscle cells in the cryo-injured rat bladder and prevent compensatory hypertrophy of surviving smooth muscle cells

PURPOSE: Wound healing of the cryo-injured bladder can bring about organ remodeling because of incomplete reconstitution of depleted smooth muscle cells. Stem cell transplantation could be beneficial to improve smooth muscle cell regeneration and/or modulate the remodeling process. The repair of bladder injury using adult-type stem cells would be useful for adult urological patients but unsuited for neonatal patients, in whom major benefits are likely to derive from fetal-type stem cells. MATERIALS AND METHODS: The smooth muscle cell differentiation potential of fetal-type vs adult-type stem cells was evaluated by injecting green fluorescent protein labeled mesenchymal stem cells from rat amniotic fluid or bone marrow, respectively, in cryo-injured rat bladder walls. RESULTS: At 30 days after transplantation only a few fetal-type or adult-type mesenchymal stem cells gave rise to enteric or vascular smooth muscle cells, whereas most mesenchymal stem cells appeared incapable of specific differentiation. In vitro co-culture experiments of smooth muscle cells with fetal-type or adult-type mesenchymal stem cells selectively labeled with distinct fluorochromes showed the presence of hybrid cells, suggesting that some mesenchymal stem cells can undergo cell fusion. Surprisingly the major effect of rat bone marrow or amniotic fluid mesenchymal stem cell transplantation seemed to be preventing cryo-injury induced hypertrophy of surviving smooth muscle cells. CONCLUSIONS: In this model stem cell transplantation has a limited effect on smooth muscle cell regeneration. Instead it can regulate post-injury bladder remodeling, possibly via a paracrine mechanism.     

Tissue Engineering der Harnblase

In tissue engineering of the urinary bladder with autologous cell transplantation, high differentiation of the cells cultivated in vitro on biocompatible membranes is essential for the functionality of the tissue constructs after implantation. The terminal differentiation of superficial urothelial cells has a key role because of the barrier function of these cells against urine. The aim of this study was to determine optimized conditions for the creation of terminally differentiated urothelium to cover large membrane surfaces. This can bring us closer to the goal of using functioning tissue constructs in clinical trials.     

Hair follicle stem cells can be driven into a urothelial‐like phenotype: An experimental study

The aim of this study was to show that conditioned medium might induce transdifferentiation of hair follicle stem cells into urothelial‐like cells. Several conditioned media and culture conditions (skeletal muscle cell conditioned medium, smooth muscle cell conditioned medium, fibroblast conditioned medium, transforming growth factor‐conditioned medium, urothelial cell conditioned medium, and co‐culture of hair follicle stem cells and urothelial cells) were used. The hair follicle stem cells phenotype from rat whisker hair follicles was checked by using flow cytometry and immunofluorescence. Cytokeratins 7, 8, 15 and 18 were used as markers. Urothelial cell conditioned medium increased the expression of urothelial markers (cytokeratin 7, cytokeratin 8, cytokeratin 18), whereas it decreased a hair follicle stem cells marker (cytokeratin 15) after 2 weeks of culture. This process depended on the time of cultivation. This medium was able to sustain the epithelial phenotype of the culture. Other media including a co‐culture system failed to induce similar changes. Smooth muscle conditioned medium resulted in a loss of cells in culture. Hair follicle stem cells are capable of differentiating into urothelial‐like cells in vitro when exposed to a bladder‐specific microenvironment.     

补肾中药对骨髓间充质干细胞成骨分化的作用研究

骨髓间充质干细胞作为骨损伤后,骨修复、重建的种子细胞,越来越成为骨组织工程学中的研究热点。骨修复、重建的关键核心是如何能够提高骨髓间充质干细胞的高效增殖和成骨定向分化。以"肾藏精,主骨,生髓"的中医理论为依据,同时实验和临床也证实,补肾中药可以有效地促进骨髓间充质干细胞增殖、以及定向成骨分化。为骨损伤之后的修复和重建提供新的治疗途径。笔者就近年补肾中药促进骨髓间充质干细胞成骨分化的研究作一综述。     

干细胞在组织工程膀胱修复中的应用

利用干细胞进行膀胱缺损修复是近年来组织工程膀胱研究的一项热点.干细胞具有自我更新和多向分化的潜能,是组织工程膀胱修复的理想种子细胞.本文分别就利用胚胎干细胞和成体干细胞作为种子细胞,进行膀胱缺损组织工程修复进行综述.     

加快创面处理领域的干细胞研究

The restoration of destroyed skin tissue in extensive deep burn injury has been perplexing burn surgeons for a long time due to impossibility of de novo formation of true skin in the process of burn wound healing with the current treatment methods. Stem cells possess the capacity to repair the damaged tissue through regeneration of the original structure and function,and it is considered as the expected ideal outcome of burn wound healing and also the final goal of multidisciplinary wound managements. In the skin tissue, the resident stem cells do exist,and they retain an autonomous self-renewal potential, and they respond to guiding signals to differentiate in repairing burn wound. Besides, the remote mesenchymal stem cells and the adjacent adipose-derived stem cells have been shown to be involved in burn wound healing. The basic studies demonstrated that the microenvironmental feature or extracellular regulators, the selective activation of intracellular signaling pathways, and the expression of specific genes have a significant influence on the proliferation, differentiation or function of stem cells in wound repair. Therefore, further investigation and manipulation of the molecular mechanisms by which stem cells could participate well in regenerating skin tissue would be a valuable and promising way in burn wound treatment. The recent discovery of reprogramming a mature body cell into a pluripotent stem cell, which can then be converted to any type of human body cell sheds a new light to regenerative medicine. Stem cell-based regeneration is offering the next coming frontier of medical therapy by yielding new treatment through delivery of pluripotent stem cells to achieve structural and functional repair in the damaged tissues or organs due to trauma or chronic diseases. Therefore, it is a pressing task for us to expedite the study on the role and utility of stem cells in burn wound treatment, especially aiming to explore the possibility in regenerating skin appendages or even the entire structure of the normal skin, and avoiding the formation of hypertrophic scar or chronic wound after burn.     

Fibroblast growth factor-7 regulates stratification of the bladder urothelium.

PURPOSE: The cellular and molecular mechanisms that regulate the organization of bladder urothelium into basal, intermediate and superficial cell layers remain poorly understood. We tested the hypothesis that fibroblast growth factor (FGF)-7 is essential for generating a multilayered stratified bladder epithelium. MATERIALS AND METHODS: The morphological and molecular characteristics of bladder urothelium in age and sex matched FGF-7 +/+ wild-type and -/- null mice were evaluated. In addition, the effect of exogenous FGF-7 on the growth and differentiation of primary murine urothelial cells was assessed. RESULTS: Morphometric analyses demonstrate that FGF-7 null urothelium is markedly thinned compared with wild-type urothelium. Electron microscopy revealed that null urothelium lacks the intermediate cell layers and molecular marker analyses confirmed this observation. In vitro cell culture experiments indicated that FGF-7 regulates urothelial cell growth, differentiation and stratification. Primary urothelial cultures maintained without FGF-7 ceased to divide and expressed proteins characteristic of terminally differentiated umbrella cells. In contrast, cultures maintained with exogenous FGF-7 contained proliferating epithelial cells with protein expression patterns consistent with those of intermediate cells in addition to terminally differentiated, post-mitotic umbrella cells. Importantly, isolated urothelial cells maintained with exogenous FGF-7 formed a multilayered epithelium in vitro. CONCLUSIONS: Collectively these data indicate that FGF-7 is essential for normal bladder urothelial stratification, specifically the formation of the intermediate cell layers. Fibroblast growth factor-7 stimulates urothelial proliferation and delays the differentiation of these cells into post-mitotic umbrella cells.     

膀胱移行细胞癌中候选肿瘤干细胞标记物USP22 mRNA水平定量分析及其与肿瘤分级的关系

目的：研究肿瘤干细胞标记物USP22 mRNA在不同级别膀胱移行细胞癌和正常膀胱黏膜中的表达差异．并探讨其与肿瘤分级,临床分期的关系。方法：分别抽提不同级别的膀胱移行细胞癌组织标本和正常膀胱黏膜组织标本的总RNA,经RT为cDNA后,采用qRT—PCR法检测USP22 mRNA的表达情况。结果：正常膀胱黏膜组织中USP22的表达明显低于膀胱肿瘤组织,几乎不表达;不同级别膀胱肿瘤组织中,低度恶性潜能的乳头状尿路上皮癌和低级尿路上皮癌中USP22的表达要明显高于其在高级尿路上皮癌中的表达;特别是Ⅲ级膀胱移行细胞癌组,USP22的表达仅略高于其在正常膀胱黏膜中的表达。结论：USP22可能是正常干细胞向肿瘤干细胞恶变的关键凋节分子,可能成为一个新的诊断移行上皮癌侵袭性的有效指标。干扰其蛋白质合成将成为一个抗肿瘤生长的新靶点。