Spring Mediated Enterogenesis

项目摘要 延长小肠是治疗因短肠引起的肠衰竭的一种潜在的治疗方法 肠道综合征。短肠综合征是影响小肠的破坏性疾病的最终结果。 短肠综合征患者有吸收不良，不能正常进食。目前的治疗方法是 短肠综合征包括提供肠外营养，优化残肠健康， 增强肠道适应能力。虽然肠外营养极大地提高了他们的存活率，但许多 短肠综合征患者不能脱离肠外营养并发展为终末期肝脏 疾病。在过去的十年里，我们开发和改进了延长小肠的装置。通过应用 逐渐用力将一段小肠与连续部分分开，我们能够将长度增加三倍 大鼠和猪的小肠。肠道细胞质量有净增长，肠道细胞数量增加。 吸收表面积。当延长的节段恢复到肠道中时，它是有功能的 连续性。这些研究证实了机械延长术作为一种新的治疗方法的潜力。 短肠综合征患者的比例。在这项拟议的研究中，我们将获得有关弹簧设备的数据，这些数据将 在不同大小的动物中延长仍处于肠道连续性的肠道。我们还将开发方法来 重复使用多个弹簧，最大限度地延长肠道。最后，我们将在一个 猪短肠模型。如果成功，这些研究将导致这些设备的第一阶段临床试验 患有短肠综合征的患者。这种方法将彻底改变慢性阻塞性肺疾病患者的治疗策略 短肠综合征。

Project Summary Lengthening the small intestine is a potentially curative therapy for patients with intestinal failure due to short bowel syndrome. Short bowel syndrome is the end result of devastating diseases that affect the small intestine. Patients with short bowel syndrome have malabsorption and cannot eat normal meals. The current therapy for short bowel syndrome consists of providing parenteral nutrition, optimizing the health of the remnant intestine, and enhancing intestinal adaptation. While parenteral nutrition has dramatically improved their survival, many patients with short bowel syndrome cannot be weaned from parenteral nutrition and develop end stage liver disease. Over the last decade, we developed and refined devices to lengthen the small intestine. By applying a gradual force to a segment of the small intestine separated from continuity, we were able to triple the length of the small intestine in rats and pigs. There was a net growth of the intestinal cell mass and an increase in the absorptive surface area. The lengthened segment was functional when it was restored back into intestinal continuity. These studies demonstrated the potential of mechanical intestinal lengthening as a novel treatment of patients with short bowel syndrome. In this proposed research, we will obtain data on spring devices that will lengthen the intestine that are still in intestinal continuity in different size animals. We will also develop ways to maximize intestinal lengthening with multiple springs applied repeatedly. Lastly, we will employ the spring in a porcine short bowel model. If successful, these studies will lead to a Phase 1 clinical trial of these devices in patients with short bowel syndrome. This approach will revolutionize the treatment strategy of patients with short bowel syndrome.