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成骨细胞与破骨细胞体外共培养模型的比较及其在临床前药物测试中的应用转化。

A Comparison of Osteoblast and Osteoclast In Vitro Co-Culture Models and Their Translation for Preclinical Drug Testing Applications.

机构信息

School of Engineering, Newcastle University, Newcastle-Upon-Tyne NE1 7RU, UK.

AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos, Switzerland.

出版信息

Int J Mol Sci. 2020 Jan 30;21(3):912. doi: 10.3390/ijms21030912.

Abstract

As the population of western societies on average ages, the number of people affected by bone remodeling-associated diseases such as osteoporosis continues to increase. The development of new therapeutics is hampered by the high failure rates of drug candidates during clinical testing, which is in part due to the poor predictive character of animal models during preclinical drug testing. Co-culture models of osteoblasts and osteoclasts offer an alternative to animal testing and are considered to have the potential to improve drug development processes in the future. However, a robust, scalable, and reproducible 3D model combining osteoblasts and osteoclasts for preclinical drug testing purposes has not been developed to date. Here we review various types of osteoblast-osteoclast co-culture models and outline the remaining obstacles that must be overcome for their successful translation.

摘要

随着西方社会人口平均年龄的增长,受骨重塑相关疾病(如骨质疏松症)影响的人数不断增加。新疗法的开发受到临床测试中候选药物高失败率的阻碍,部分原因是临床前药物测试中动物模型的预测特征较差。成骨细胞和破骨细胞的共培养模型为动物测试提供了替代方法,并被认为有可能在未来改善药物开发过程。然而,迄今为止,尚未开发出用于临床前药物测试目的的稳健、可扩展和可重复的结合成骨细胞和破骨细胞的 3D 模型。在这里,我们回顾了各种类型的成骨细胞-破骨细胞共培养模型,并概述了为成功转化它们必须克服的剩余障碍。

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