Engineering in-vitro stem cell-based vascularized bone models for drug screening and predictive toxicology.
Engineering in-vitro stem cell-based vascularized bone models for drug screening and predictive toxicology.
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DOI：
10.1186/s13287-018-0847-8
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发表时间：
2018-04-20
影响因子：
7.5
通讯作者：
Tuan RS
中科院分区：
文献类型：
--
作者：
Pirosa A;Gottardi R;Alexander PG;Tuan RS
建立真实的骨组织体外模型对于了解骨及其周围环境的生物学、分析骨疾病(如骨质疏松、骨关节炎、骨髓炎等)的发病机制、开发有效的治疗药物筛选和测试潜在的治疗策略是必不可少的。血管系统和骨细胞之间的失调相互作用通常与上述病理有关，强调了包含工程化血管系统的骨模型的必要性。由于伦理的限制和动物模型有限的预测能力，基于人类干细胞的组织工程作为一种克服动物局限性和作为药物试验的临床前模型的候选方法已经获得了越来越多的相关性。由于骨是一种高度血管化的组织，血管形成和矿化基质的伴随发展需要成骨和内皮前体之间的协同作用。为了实现这一目标，已经使用了许多实验方法，如血管生成因子和三维支架的组合，预血管形成策略，以及共培养系统。在这篇综述中，我们概述了目前基于干细胞的体外血管化骨生成的模型和方法，重点介绍了血管工程的主要挑战。这些挑战涉及到生物材料、支架制造技术和细胞的选择，以及所需培养条件的类型，特别是使用生物反应器的动态培养系统的应用。
The production of veritable in-vitro models of bone tissue is essential to understand the biology of bone and its surrounding environment, to analyze the pathogenesis of bone diseases (e.g., osteoporosis, osteoarthritis, osteomyelitis, etc.), to develop effective therapeutic drug screening, and to test potential therapeutic strategies. Dysregulated interactions between vasculature and bone cells are often related to the aforementioned pathologies, underscoring the need for a bone model that contains engineered vasculature. Due to ethical restraints and limited prediction power of animal models, human stem cell-based tissue engineering has gained increasing relevance as a candidate approach to overcome the limitations of animals and to serve as preclinical models for drug testing. Since bone is a highly vascularized tissue, the concomitant development of vasculature and mineralized matrix requires a synergistic interaction between osteogenic and endothelial precursors. A number of experimental approaches have been used to achieve this goal, such as the combination of angiogenic factors and three-dimensional scaffolds, prevascularization strategies, and coculture systems. In this review, we present an overview of the current models and approaches to generate in-vitro stem cell-based vascularized bone, with emphasis on the main challenges of vasculature engineering. These challenges are related to the choice of biomaterials, scaffold fabrication techniques, and cells, as well as the type of culturing conditions required, and specifically the application of dynamic culture systems using bioreactors.
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影响因子：
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作者：
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通讯作者：
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DOI：
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发表时间：
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期刊：
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通讯作者：
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DOI：
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发表时间：
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影响因子：
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