Kitamura Koji, von Websky Martin W, Ohsawa Ichiro, Jaffari Azin, Pech Thomas C, Vilz Tim, Wehner Sven, Uemoto Shinji, Kalff Joerg C, Schaefer Nico
Department of Surgery, University of Bonn, Germany.
J Vis Exp. 2012 Nov 6(69):4102. doi: 10.3791/4102.
Small bowel transplantation has become an accepted clinical option for patients with short gut syndrome and failure of parenteral nutrition (irreversible intestinal failure). In specialized centers improved operative and managing strategies have led to excellent short- and intermediate term patient and graft survival while providing high quality of life (1,3). Unlike in the more common transplantation of other solid organs (i.e. heart, liver) many underlying mechanisms of graft function and immunologic alterations induced by intestinal transplantation are not entirely known(6,7). Episodes of acute rejection, sepsis and chronic graft failure are the main obstacles still contributing to less favorable long term outcome and hindering a more widespread employment of the procedure despite a growing number of patients on home parenteral nutrition who would potentially benefit from such a transplant. The small intestine contains a large number of passenger leucocytes commonly referred to as part of the gut associated lymphoid system (GALT) this being part of the reason for the high immunogenity of the intestinal graft. The presence and close proximity of many commensals and pathogens in the gut explains the severity of sepsis episodes once graft mucosal integrity is compromised (for example by rejection). To advance the field of intestinal- and multiorgan transplantation more data generated from reliable and feasible animal models is needed. The model provided herein combines both reliability and feasibility once established in a standardized manner and can provide valuable insight in the underlying complex molecular, cellular and functional mechanisms that are triggered by intestinal transplantation. We have successfully used and refined the described procedure over more than 5 years in our laboratory (8-11). The JoVE video-based format is especially useful to demonstrate the complex procedure and avoid initial pitfalls for groups planning to establish an orthotopic rodent model investigating intestinal transplantation.
小肠移植已成为短肠综合征和肠外营养失败（不可逆性肠衰竭）患者可接受的临床选择。在专业中心，改进的手术和管理策略已使患者和移植物在短期和中期获得了优异的存活率，同时提供了高质量的生活（1,3）。与其他实体器官（如心脏、肝脏）更常见的移植不同，肠道移植诱导的移植物功能和免疫改变的许多潜在机制尚不完全清楚（6,7）。急性排斥反应、败血症和慢性移植物衰竭仍是主要障碍，尽管越来越多接受家庭肠外营养的患者可能从这种移植中受益，但这些障碍仍导致长期预后不佳，并阻碍了该手术的更广泛应用。小肠含有大量通常被称为肠道相关淋巴系统（GALT）一部分的过客白细胞，这是肠道移植物免疫原性高的部分原因。肠道中许多共生菌和病原体的存在及其密切 proximity 解释了一旦移植物黏膜完整性受损（例如通过排斥反应）败血症发作的严重性。为了推进肠道和多器官移植领域，需要从可靠且可行的动物模型中获得更多数据。本文提供的模型一旦以标准化方式建立，就兼具可靠性和可行性，并能为肠道移植触发的潜在复杂分子、细胞和功能机制提供有价值的见解。我们在我们的实验室中已成功使用并完善所描述的程序超过5年（8-11）。基于JoVE视频的格式对于展示复杂程序以及避免计划建立研究肠道移植的原位啮齿动物模型的团队最初的陷阱特别有用。
