Sato M, Keshavjee S, Liu M
Latner Thoracic Research Laboratories, Toronto General Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Am J Transplant. 2009 Sep;9(9):1981-7. doi: 10.1111/j.1600-6143.2009.02770.x. Epub 2009 Aug 6.
Obliterative bronchiolitis (OB) or chronic graft dysfunction remains the major limitation to long-term success of lung transplantation. Investigation using animal models is a critical component of research to understand the underlying pathological mechanisms and to develop novel preventive and therapeutic strategies for OB. Multiple animal models of OB exist, including orthotopic lung transplantation in rodents and large animals, orthotopic tracheal transplantation and heterotopic transplantation of a trachea in variable sites such as subcutaneous, intraomental and intrapulmonary sites. The most important issue for researchers is not specifically which model is the best but which is the most appropriate model to test their scientific hypothesis. For example, while orthotopic lung transplantation best mimics the overall surgical procedure, a question regarding fibrotic processes of OB may be better answered using heterotopic tracheal transplant models because of their reliable reproducibility of allograft obliterative airway fibrosis. Animal models should be continuously refined, modified and sometimes combined to fit the particular research purpose. We review the available animal models, their modifications and possible applications to assist researchers in choosing the appropriate model for their intended research.
闭塞性细支气管炎(OB)或慢性移植功能障碍仍然是肺移植长期成功的主要限制因素。利用动物模型进行研究是了解潜在病理机制以及开发针对OB的新型预防和治疗策略的关键研究组成部分。存在多种OB动物模型,包括啮齿动物和大型动物的原位肺移植、原位气管移植以及在皮下、网膜内和肺内等不同部位进行的气管异位移植。对于研究人员来说,最重要的问题不是哪种模型是最好的,而是哪种模型最适合检验他们的科学假设。例如,虽然原位肺移植最能模拟整个手术过程,但由于其同种异体移植闭塞性气道纤维化的可靠可重复性,关于OB纤维化过程的问题可能使用异位气管移植模型能得到更好的解答。动物模型应不断完善、改进,有时还需组合使用,以适应特定的研究目的。我们综述了现有的动物模型、它们的改进以及可能的应用,以帮助研究人员为其预期研究选择合适的模型。