PDF(Pubmed)
Abstract：
Intestinal failure (IF) occurs when intestinal surface area or function is not sufficient to support digestion and nutrient absorption. Human intestinal organoid (HIO)-derived tissue-engineered intestine is a potential cure for IF. Research to date has demonstrated successful HIO transplantation (tHIO) into mice with significant in vivo maturation. An area lacking in the literature is exploration of murine host sex as a biological variable (SABV) in tHIO function. In this study, we investigate murine host SABV in tHIO epithelial barrier function and muscle contractility. HIOs were generated in vitro and transplanted into nonobese diabetic, severe combined immunodeficiency gamma chain deficient male and female mice. tHIOs were harvested after 8-12 weeks in vivo. Reverse transcriptase polymerase chain reaction and immunohistochemistry were conducted to compare tight junctions and contractility-related markers in tHIOs. An Ussing chamber and contractility apparatus were used to evaluate tHIO epithelial barrier and muscle contractile function, respectively. The expression and morphology of tight junction and contractility-related markers from tHIOs in male and female murine hosts is not significantly different. Epithelial barrier function as measured by transepithelial resistance, short circuit current, and fluorescein isothiocyanate-dextran permeability is no different in tHIOs from male and female hosts, although these results may be limited by HIO epithelial immaturity and a short flux time. Muscle contractility as measured by total contractile activity, amplitude, frequency, and tension is not significantly different in tHIOs from male and female hosts. The data suggest that murine host sex may not be a significant biological variable influencing tHIO function, specifically epithelial barrier maintenance and muscle contractility, though limitations exist in our model.
摘要：
当肠表面积或功能不足以支持消化和营养吸收时,发生肠衰竭(IF)。人类肠道类器官（HIO）来源的组织工程肠是IF的潜在治疗方法。迄今为止的研究已经证明成功的HIO移植(tHIO)到具有显著体内成熟的小鼠中。文献中缺乏的领域是探索鼠宿主性别作为tHIO功能中的生物学变量（SABV）。在这项研究中,我们研究了鼠宿主SABV中的tHIO上皮屏障功能和肌肉收缩性。HIOs在体外产生并移植到非肥胖糖尿病患者中，严重的联合免疫缺陷γ链缺乏的雄性和雌性小鼠。在体内8-12周后收获tHIOs。进行逆转录酶聚合酶链反应和免疫组织化学以比较tHIOs中的紧密连接和收缩性相关标志物。使用Ussing室和收缩装置评估THIO上皮屏障和肌肉收缩功能，分别。tHIOs在雄性和雌性鼠宿主中的紧密连接和收缩性相关标记的表达和形态没有显着差异。通过跨上皮阻力测量的上皮屏障功能，短路电流,异硫氰酸荧光素-葡聚糖的通透性在tHIOs中与雄性和雌性宿主没有差异，尽管这些结果可能受到HIO上皮不成熟和较短的通量时间的限制。通过总收缩活动测量的肌肉收缩力，振幅,频率,tHIOs与男性和女性宿主的张力没有显着差异。数据表明，鼠宿主性别可能不是影响tHIO功能的重要生物学变量，特别是上皮屏障维持和肌肉收缩，尽管我们的模型存在局限性。
