弹簧介导的分心肠生成可能会改变猪短肠综合征的适应过程

Geoanna Bautista, Genia Dubrovsky, Nicolle K. Sweeney, R. Solórzano-Vargas, Daniel J. Tancredi, Michael Lewis, Mattias Stelzner, Martín G. Martín, J. C. Dunn
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摘要

严重的短肠综合征(SBS)会导致慢性肠功能衰竭(IF),但目前的治疗方法有限,而且所有这些治疗方法都与严重的发病率有关。弹簧介导的牵张肠道生成术(SMDE)利用腔内自膨胀弹簧产生机械力,诱导肠道伸展和持续的轴向生长,为SBS患者提供了一种前景广阔的新方法。以往的研究已证实这种方法在小型和大型动物模型中安全有效。切除了 75% 小肠的幼年小尤卡坦猪在最初的适应期后被放置了腔内弹簧。对 SMDE 区段进行了形态学和组织学评估,并将其与正常适应切除反应的肠道对照区进行了比较。一个月后,切除后观察到的最初组织学适应反应有所减弱,但 SMDE 区段反而增强了这些适应性变化。具体来说,与同一动物的对照组相比,SMDE 节段的肠道长度增加了 2 倍,上皮、肌层和浆膜层的宽度也增加了。这些数据表明,在 SBS 的情况下,SMDE 可增强肠道的形态适应性。在此,我们证明了在大型动物模型中,在先前进行过肠道切除的情况下,SMDE 的成功实施和可重复性,使 SMDE 成为治疗 SBS 的一种可行的新方法,有待进一步探索。
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Spring-mediated distraction enterogenesis may alter the course of adaptation in porcine short bowel syndrome
Severe forms of short bowel syndrome (SBS) resulting in chronic intestinal failure (IF) have limited therapeutic options, all of which are associated with significant morbidities. Spring-mediated distraction enterogenesis (SMDE) uses an intraluminal self-expanding spring to generate mechanical force to induce intestinal stretching and sustained axial growth, providing a promising novel approach for patients with SBS. Previous studies have established this method to be safe and effective in small and large animal models. However, SMDE has previously not been implemented in a large, clinically relevant animal model.Juvenile mini-Yucatan pigs with 75% of their small intestine resected had intraluminal springs placed after an initial adaptive period. Morphological and histological assessments were performed on SMDE segments compared to the control region of the intestine undergoing normal adaptive responses to resection.While the initial histologic adaptive response observed following resection was attenuated after a month, the SMDE segments instead augmented these adaptive changes. Specifically, intestinal length increased 2-fold in SMDE segments, and the widths of the epithelial, muscularis, and serosal layers were enhanced in SMDE compared with control segments of the same animal. This data suggests that morphologic intestinal adaptation may be enhanced with SMDE in the setting of SBS.Here we demonstrate the successful and reproducible implementation of SMDE in a large animal model in the setting of prior intestinal resection, making SMDE a viable and novel approach for SBS to be explored further.
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