Spring Mediated Enterogenesis

项目摘要 延长小肠是一种潜在的治疗肠衰竭的患者由于短 肠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。目前治疗 短肠综合征包括提供肠外营养，优化残肠的健康， 和增强肠道适应性。虽然肠外营养极大地提高了他们的生存率，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设备。通过施加 逐渐的力量，以一段小肠分离的连续性，我们能够三倍的长度， 老鼠和猪的小肠。有一个净增长的肠细胞质量和增加， 吸收表面积延长段回肠后功能恢复正常 连续性这些研究证明了机械性肠延长作为一种新型治疗方法的潜力 短肠综合征的患者。在这项拟议的研究中，我们将获得弹簧装置的数据， 在不同大小的动物中，延长仍处于肠道连续性的肠道。我们还将制定方法， 通过反复应用多个弹簧来最大化肠延长。最后，我们将使用弹簧， 猪短肠模型。如果成功，这些研究将导致这些设备的1期临床试验， 短肠综合征患者。这种方法将彻底改变患者的治疗策略， 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.