由于缺乏理想的人源性肿瘤骨转移动物模型，乳腺癌骨转移途径及分子机制尚不明确。而小鼠和人类之间存在的巨大种属差异，导致目前的小鼠异种移植肿瘤模型不利于乳腺癌骨转移机制及药物筛查的研究。本课题将组织工程原理和研究手段引入人源性乳腺癌骨转移小鼠模型的构建中，拟建立人源化的CAFs成纤维细胞库，并将人源化的CAFs成纤维细胞与弹性梯度材料复合培养制备三维饲养层，在该饲养层上构建三维乳腺癌组织，用作原发灶肿瘤植入体；同时，采用人同种异体骨制备多孔的BMP-2偶联的不完全脱钙骨，采用人源性的骨髓间充质干细胞与脱钙骨制备用于移植的人源性组织工程骨，用作骨组织植入体；在构建的三维人源化乳腺癌组织和骨组织的基础上，建立乳腺癌骨转移裸鼠模型。并基于该动物模型研究乳腺癌骨转移的组织形态学、影像学以及相关细胞的变化；探讨相关内环境变化的分子机制，为乳腺癌骨转移模式化小鼠模型的建立及其标准化提供研究基础和技术支持。

Due to lack of an ideal human source breast cancer animal model, the bone metastasis pathway and its molecular mechanism has not yet been illustrated clearly. The giant species difference between mouse and human leads to the difficult on the study of breast cancer bone metastasis mechanism and drug screening. Here, the tissue engineering principles and techniques will be introduced into the building of human source breast cancer bone metastasis mouse model. We try to establish humanized CAFs fibroblast cells bank. The humanized CAFs fibroblasts and flexibility gradient material will be used for preparing three-dimensional feeder layer, then the human breast cancer cells will be seeded on it. The human 3D breast cancer tissue will be constructed through the three-dimensional culture system and taken as the primary tumor implants. At the same time, BMP-2 coupling porous human allogeneic decalcified bone and human derived bone marrow mesenchymal stem cells will be used to construct engineering human bone tissue, and taken as a source of human bone tissue implan. The purpose of this project is to establish the nude mice models of breast cancer bone metastasis. The changes of morphology, image of bone metastasis of breast and bone metastasis related cells of this kind of animal models will be detected. The related bone metastasis molecular mechanisms will be also explored. This project will provide excellent technical support and research foundation for the establishment and standardization of human breast cancer bone metastasis mouse model.