Pierce Angela M, Keating Amy K
Department of Pediatrics, University of Colorado School of Medicine.
Department of Pediatrics, University of Colorado School of Medicine;
J Vis Exp. 2014 Sep 24(91):52017. doi: 10.3791/52017.
Orthotopic tumor models are currently the best way to study the characteristics of a tumor type, with and without intervention, in the context of a live animal - particularly in sites with unique physiological and architectural qualities such as the brain. In vitro and ectopic models cannot account for features such as vasculature, blood brain barrier, metabolism, drug delivery and toxicity, and a host of other relevant factors. Orthotopic models have their limitations too, but with proper technique tumor cells of interest can be accurately engrafted into tissue that most closely mimics conditions in the human brain. By employing methods that deliver precisely measured volumes to accurately defined locations at a consistent rate and pressure, mouse models of human brain tumors with predictable growth rates can be reproducibly created and are suitable for reliable analysis of various interventions. The protocol described here focuses on the technical details of designing and preparing for an intracranial injection, performing the surgery, and ensuring successful and reproducible tumor growth and provides starting points for a variety of conditions that can be customized for a range of different brain tumor models.
原位肿瘤模型是目前在活体动物体内研究肿瘤类型特征（无论有无干预）的最佳方法，尤其是在具有独特生理和结构特性的部位，如大脑。体外和异位模型无法考虑诸如脉管系统、血脑屏障、代谢、药物递送和毒性等特征以及许多其他相关因素。原位模型也有其局限性，但通过适当的技术，可以将感兴趣的肿瘤细胞准确地植入最接近模拟人类大脑状况的组织中。通过采用以一致的速率和压力将精确测量的体积输送到精确界定位置的方法，可以可重复地创建具有可预测生长速率的人脑肿瘤小鼠模型，并且适合于对各种干预措施进行可靠分析。这里描述的方案侧重于设计和准备颅内注射、进行手术以及确保肿瘤成功且可重复生长的技术细节，并为一系列不同脑肿瘤模型可定制的各种情况提供了起点。
