Small animal models of experimental obliterative bronchiolitis

Despite significant progress in the treatment of chronic lung allograft rejection, obliterative bronchiolitis (OB) remains the major limitation to long-term survival after lung transplantation. The use of animal models is critical to an understanding of the pathological mechanisms behind OB, and to develop therapeutic strategies for OB. For almost 20 years, the technique of heterotopic tracheal transplantation was the leading experimental model in OB research. To address the need for a more physiologic experimental setup, a variety of small animal models have been proposed during the past two decades, such as the orthotopic tracheal transplantation model or the intrapulmonary trachea implantation model. The recent introduction of the orthotopic lung transplantation model in the mouse fulfilled the criteria for a physiologic lung transplantation setup, and also presents the advantage of being genetically modifiable. Here we review the evolution of OB models and their applications, from their beginning to the rapidly emerging physiologic models of chronic lung allograft rejection.