Tissue Engineered Intestine

组织工程肠

• 批准号: 8979048
• 负责人: Jed Kizer Johnson
• 金额: $ 22.5万
• 依托单位: NANOFIBER SOLUTIONS, LLC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8979048
• 关键词: Abdominal Cavity; Actins; Adult; Affect; Age; Anatomy; Animal Model; Animals; Anterior; Catheters; Cell Separation; Cells; Cessation of life; Child; Chromogranin A; Clinic; Clinical; Data; Development; Diarrhea; Disease; Electrolytes; Enteric Nervous System; Enterocytes; Enteroendocrine Cell; Filtration; Goblet Cells; Greater sac of peritoneum; Harvest; Height; Home Total Parenteral Nutrition; Immunosuppression; Implant; Intestines; Laboratories; Length; Licensing; Life; Liquid substance; Malabsorption Syndromes; Malnutrition; Medical; Methodology; Methods; Mucous body substance; Necrotizing Enterocolitis; Newborn Infant; Omentum; Organoids; Patients; Pediatric Hospitals; Periodic acid Schiff stain method; Peristalsis; Phase; Play; Premature Infant; Procedures; Production; Proliferating; Rattus; Role; Short Bowel Syndrome; Small Business Innovation Research Grant; Small Intestines; Smooth Muscle; Smooth Muscle Myocytes; Societies; Solutions; Staining method; Stains; Steatorrhea; Stem cells; Structure; Surgical sutures; Survival Rate; Techniques; Technology; Thick; Tissue Engineering; Total Parenteral Nutrition; Translations; Transplantation; Venous; Villous; Villus; Work; abdominal wall; base; commercialization; cost; in vivo; mortality; nanofiber; nerve stem cell; nerve supply; nervous system development; novel; novel strategies; public health relevance; scaffold; scale up; success; villin

 DESCRIPTION (provided by applicant): Short bowel syndrome (SBS), a major clinical problem affecting patients of all ages, results from the functional or anatomic loss of extensive segments of small intestine. SBS has an overall 5-year survival of 70%, and in newborn infants with less than 10% of expected intestinal length, 5-year survival is only 20%. Current treatment options are inadequate and associated with severe complications and death. Patients with SBS require total parenteral nutrition (TPN) to survive. Currently, over 20,000 SBS patients per year are on home TPN in the US alone. Annual costs of home TPN exceed $300,000 per year per patient ($6 billion/year). In addition the use of TPN is associated with numerous central venous catheter-associated infectious and thrombotic complications, resulting in additional high costs. Thus, SBS represents an extremely costly, and deadly, burden to society. At present, the treatment for SBS is mainly supportive. Although small bowel transplantation is an option, the results are suboptimal, with 1-year and 4-year survival rates of 90% and 60%, respectively, and the required life-long immunosuppression causes substantial secondary complications. Novel approaches for the treatment of patients with SBS are critically needed. Our approach to this unsolved medical problem is the production of tissue-engineered intestine (TEI) using the patient's own intestinal cells combined with a synthetic nanofiber-based scaffold, resulting in a novel solution to this unmet clinical need. In this project, we will accomplish three specific aims necessary to move towards commercialization: Aim 1) Determine the optimal cell isolation and cell seeding methodology for structural formation of TEI. Aim 2) Optimize enteric nervous system (ENS) development in TEI. Aim 3) Develop an in vivo culture standard operating procedure (SOP) for development of TEI. This Phase I SBIR project will allow us to collect the pivotal data needed to scale up to a large animal model in Phase II, and to license the technology to a commercial partner in Phase III for commercialization.

 简介(申请人提供)：短肠综合征(SBS)是一种影响所有年龄段患者的主要临床问题，由广泛的小肠节段的功能或解剖丢失所致。SBS的总体5年存活率为70%，而在肠道长度低于预期长度10%的新生儿中，5年存活率仅为20%。目前的治疗方案不足，并与严重的并发症和死亡有关。SBS患者需要完全肠外营养(TPN)才能存活。目前，仅在美国，每年就有超过2万名SBS患者在家中接受TPN治疗。家庭TPN的年成本超过每个患者每年300,000美元(60亿美元/年)。此外，TPN的使用与许多中心静脉导管相关的感染和血栓并发症有关，导致额外的高成本。因此，SBS对社会来说是一个极其昂贵和致命的负担。目前，对SBS的治疗主要是支持性的。虽然小肠移植是一种选择，但结果并不理想，1年和4年存活率分别为90%和60%，所需的终身免疫抑制会导致大量的继发性并发症。迫切需要治疗SBS患者的新方法。我们解决这一悬而未决的医学问题的方法是使用患者自身的肠道细胞与合成纳米纤维支架相结合来生产组织工程肠(TEI)，从而为这一未得到满足的临床需求提供了一种新的解决方案。在这个项目中，我们将实现三个具体目标 走向商业化所必需的：目的1)确定形成TEI结构的最佳细胞分离和细胞接种方法。目的2)优化TEI中肠神经系统的发育。目的3)建立体内培养标准操作程序(SOP)，用于TEI的研制。这个第一阶段的SBIR项目将允许我们收集在第二阶段扩大到大型动物模型所需的关键数据，并在第三阶段将技术许可给商业合作伙伴进行商业化。