Construction Of The Humanized Breast Cancer-bone Metastasis Mouse Model Based On Bone Tissue Engineering

BackgroundBreast cancer is one of the most common tumors around the world and has the propensity to spread to other organs.Among which,bone metastasis has the highest frequency and can lead to a lot of serious complications to patients.At present,the molecular mechanism of breast cancer bone metastasis is not clear and the current treatment efficacy is poor.Many efforts have been devoted to dealing with the problem.Appropriate bone metastasis animal models are urgently needed to study the potent mechanisms about breast cancer's metastasizing to the bone and do the drug screening.However,the construction of the humanized mouse model for breast cancer bone metastasis which can mimick real interactions between cancer tissue and bone tissue in the human microenvironment remains a challenge.ObjectiveEstablishing a humanized breast cancer bone metastasis animal model based on tissue engineering to better study the molecular mechanisms and facilitate drug screening.Methods1.Preparation of silica nanoparticles-incorporated human demineralized bone matrix.We studied the characterization,performance,and cell interaction of the silica nanoparticles-incorporated human demineralized bone matrix.2.We constructed a human engineering bone tissue composed with the human osteoblast-like cells and the silica nanoparticles-incorporated human demineralized bone matrix and futher study its osteoinductive ability in vivo and in vitro.3.After transplanting the human engineering bone tissue into the nude mouse,the human breast cancer cells were then injected under the armpit of the nude mouse to form an orthotopic tumor and the humanized mouse model for breast cancer bone metastasis was constructed.Results1.The size distributions of the silica nanoparticles varied from 100 nm to 150 nm and exhibited a regular spherical shape.Silica nanoparticles were well-seperated on the surface of human demineralized bone matrix.Silica nanoparticles incorporated human demineralized bone matrix had excellent biocompatibility.2.Compared with human demineralized bone matrix,silica nanoparticles incorporated human demineralized bone matrix had a stronger osteoinductive ability,which could obviously up-regulate the expression of some osteogenic-related proteins and form more new bone tissue in vivo.3.Two weeks after the injection of human breast cancer cells under the armpit of the engineering bone tissue transplanted nude mouse,the breast cancer cells were found to migrate in the engineering bone tissue.ConclusionIn this study,we constructed a human engineering bone tissue composed with the human osteoblast-like cells and the silica nanoparticles-incorporated human demineralized bone matrix based on tissue engineering and successfully constructed a humanized mouse model for breast cancer bone metastasis.