The use of murine embryonic stem cells, alginate encapsulation, and rotary microgravity bioreactor in bone tissue engineering
The use of murine embryonic stem cells, alginate encapsulation, and rotary microgravity bioreactor in bone tissue engineering
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DOI：
10.1016/j.biomaterials.2008.07.028
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发表时间：
2009-02-01
期刊：
影响因子：
14
通讯作者：
Mantalaris, Athanasios
中科院分区：
文献类型：
--
作者：
Hwang, Yu-Shik;Cho, Johann;Mantalaris, Athanasios
胚胎干细胞（ESC）在骨组织工程和再生医学中的应用需要开发合适的生物过程，其促进临床相关的、可规模化的和整合的生物过程的整合的、可再现的、可自动配对的生产，所述生物过程产生足够的细胞数量，导致形成三维（3D）矿化的、单组织样构建体。以前，我们已经报道了在没有胚状体形成的情况下，未分化的mESCs向成骨谱系的分化增强。在此，我们提出了一个有效的和集成的三维生物过程的基础上封装的未分化的胚胎干细胞在藻酸盐水凝胶和培养在旋转细胞培养微重力生物反应器。具体地，对于前3天，将包封的mESC在50%（v/v）HepG 2条件培养基中培养以产生具有增强的中胚层分化能力的细胞群，随后使用含有抗坏血酸、β-甘油磷酸盐和地塞米松的成骨培养基进行成骨分化。生成3D矿化构建体，其显示成骨谱系的形态、表型和分子属性，以及机械强度和矿化钙/磷酸盐沉积。因此，这种生物过程提供了一种有效的、可自动化的、可扩展的和功能性的培养系统，用于在宏观骨形成的背景下应用于骨组织工程。(C)2008年由Elsevier Ltd.出版
The application of embryonic stem cells (ESCs) in bone tissue engineering and regenerative medicine requires the development of suitable bioprocesses that facilitate the integrated, reproducible, auto-matable production of clinically-relevant, scaleable, and integrated bioprocesses that generate sufficient cell numbers resulting in the formation of three-dimensional (3D) mineralised,])one tissue-like constructs. Previously, we have reported the enhanced differentiation of undifferentiated mESCs toward the osteogenic lineage in the absence of embryoid body formation. Herein, we present an efficient and integrated 3D bioprocess based on the encapsulation of undifferentiated mESCs within alginate hydrogels and culture in a rotary cell culture microgravity bioreactor. Specifically, for the first 3 days, encapsulated mESCs were Cultured in 50% (v/v) HepG2 conditioned medium to generate a cell Population with enhanced mesodermal differentiation capability followed by osteogenic differentiation using osteogenic media containing ascorbic acid, beta-glycerophosphate and dexamethasone. 3D mineralised constructs were generated that displayed the morphological, phenotypical, and molecular attributes of the osteogenic lineage, as well mechanical strength and mineralised calcium/phosphate deposition. Consequently, this bioprocess provides an efficient, automatable, scalable and functional Culture system for application to bone tissue engineering in the context of macroscopic bone formation. (C) 2008 Published by Elsevier Ltd.