Spring Mediated Enterogenesis

春季介导的肠发生

• 批准号: 10491119
• 负责人: James C Dunn
• 金额: $ 35.45万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-21 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10491119
• 关键词: Affect; Animal Model; Animals; Area; Back; Caliber; Cells; Clinical; Clinical Trials; Coiled Springs; Data; Devices; Dimensions; Disease; Eating; Excision; Failure; Family suidae; Goals; Growth; Health; Health Care Costs; Intestinal Obstruction; Intestinal Perforation; Intestines; Intravenous; Lead; Length; Liver Failure; Malabsorption Syndromes; Measures; Mechanics; Mediating; Modeling; Operative Surgical Procedures; Parenteral Nutrition; Patient Care; Patients; Phase I Clinical Trials; Positioning Attribute; Rattus; Research; Research Proposals; Residual state; Rodent; Rodent Model; Safety; Short Bowel Syndrome; Small Intestines; Supportive care; Surface; Surgical sutures; Techniques; United States; Weaning; Work; curative treatments; distraction; end stage liver disease; improved; improved functioning; innovation; jejunum; mechanical device; nitinol; novel; nutrition; porcine model; preclinical study; scale up; treatment strategy

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.

项目概要 延长小肠对于因短肠而导致肠衰竭的患者来说是一种潜在的治疗方法 肠综合症。短肠综合症是影响小肠的破坏性疾病的最终结果。 短肠综合症患者存在吸收不良，无法正常进食。目前的治疗方法为 短肠综合征包括提供肠外营养、优化残余肠道的健康、 并增强肠道适应。虽然肠外营养极大地提高了他们的生存率，但许多人 短肠综合征患者无法戒断肠外营养并发展为终末期肝脏 疾病。在过去的十年中，我们开发并改进了延长小肠的设备。通过应用 逐渐对一段与连续性分离的小肠施力，我们能够将长度增加三倍 大鼠和猪的小肠。肠细胞团出现净增长，并且 吸收表面积。当延长的部分恢复到肠道中时，它就发挥了功能 连续性。这些研究证明了机械肠延长作为一种新型治疗方法的潜力 短肠综合征患者。在这项拟议的研究中，我们将获得有关弹簧装置的数据，这些数据将 延长不同体型动物仍保持肠道连续性的肠道。我们还将开发方法 通过反复应用多个弹簧，最大限度地延长肠道。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在 短肠综合症患者。这种方法将彻底改变患者的治疗策略 短肠综合症。