Merl Sarah, Chen Bryan, Gunes M Esad, Atta Hussein, Yang Kryscilla, Ekanayake-Alper Dilrukshi, Hajosi Dominik, Huang Fei, Bhola Brittany, Patwardhan Satyajit, Jordache Philip, Nowak Greg, Martinez Mercedes, Kato Tomoaki, Sykes Megan, Yamada Kazuhiko, Weiner Joshua
Columbia Center for Translational Immunology, Columbia University, New York, NY, United States.
Department of Pathology and Cell Biology, Columbia University, New York, NY, United States.
Front Transplant. 2024 May 2;3:1367486. doi: 10.3389/frtra.2024.1367486. eCollection 2024.
Intestinal transplantation (ITx) is the last remaining therapy for patients with intestinal failure once parenteral nutrition is no longer an option, however its use is limited by immunological complications, including high rates of rejection and morbidity associated with immunosuppression, such as infection and malignancy. We aimed to develop a large animal model of ITx with which to study the immune response to ITx and to design and test tolerance induction regimens.
Learning from prior complications, we developed and progressively improved both surgical methods for the donor and recipient as well as postoperative management strategies. Methods of stoma generation, bowel positioning, vessel preparation, and fluid management were optimized. The immunosuppression strategy mirrored our clinical regimen.
As a result of our modifications, results improved from survival less than 1 month to consistent long-term survival with good graft function. We review several techniques that were developed to avoid pitfalls that were encountered, which can be used to optimize outcomes in this model.
Achieving long-term survival after swine orthotopic ITx permits immunological analysis and pre-clinical trials in a large animal model of ITx.
对于肠衰竭患者，一旦肠外营养不再可行，肠移植（ITx）是最后一种可用的治疗方法，然而其应用受到免疫并发症的限制，包括高排斥率以及与免疫抑制相关的发病率，如感染和恶性肿瘤。我们旨在建立一种ITx的大型动物模型，用于研究对ITx的免疫反应，并设计和测试诱导耐受方案。
借鉴先前的并发症经验，我们开发并逐步改进了供体和受体的手术方法以及术后管理策略。优化了造口形成、肠管定位、血管准备和液体管理方法。免疫抑制策略与我们的临床方案一致。
通过我们的改进，结果从存活时间不足1个月改善为长期存活且移植物功能良好。我们回顾了为避免所遇到的陷阱而开发的几种技术，这些技术可用于优化该模型的结果。
在猪原位ITx后实现长期存活，使得在ITx大型动物模型中进行免疫分析和临床前试验成为可能。
