Computational modeling for the optimization of a cardiogenic 3D bioprocess of encapsulated embryonic stem cells
Computational modeling for the optimization of a cardiogenic 3D bioprocess of encapsulated embryonic stem cells
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DOI：
10.1007/s10237-011-0308-0
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发表时间：
2012-01-01
影响因子：
3.5
通讯作者：
Morbiducci, U.
中科院分区：
文献类型：
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作者：
Consolo, F.;Bariani, C.;Morbiducci, U.
我们提出了一个基于计算流体力学(CFD)的模型，旨在确定在旋转生物反应器中促进水凝胶微珠包裹的胚胎干细胞(ESCs)高效心脏形成的最佳培养条件。该数值方法集成了扩散、对流和多相流体动力学计算，可以评估(I)漂珠的微重力运动，(Ii)向细胞输送O-2，以及(Iii)考虑细胞对O(2)的消耗，作为培养室不同转速的函数。根据我们的结果，25rpm的旋转(I)增强了细胞载体的充分混合，避免了沉淀和过度堆积，也保持了悬浮珠的相当均匀的分布，(Ii)提供了适当的细胞氧气供应，使细胞接近常氧条件。数值分析得出的生物反应器工作条件允许在体外获得长期的细胞活性维持，支持通过基于化学的条件生物过程高效大规模地产生胚胎干细胞来源的心肌细胞(ESC-DC)。总之，我们论证了使用基于CFD的工具作为一种可靠且经济高效的策略来辅助设计3D心源性生物过程的可行性。
We present a computational fluid dynamics (CFD)-based model aimed at the identification of optimized culture conditions promoting efficient cardiogenesis of hydrogel-bead-encapsulated embryonic stem cells (ESCs) within a rotating bioreactor. The numerical approach, integrating diffusion, convection, and multiphase fluid dynamics calculations, allowed to evaluate (i) the microgravity motion of the floating beads, (ii) the O-2 delivery to the cells, also (iii) taking into account the cellularO(2) consumption, as a function of different rotation speeds of the breeding chamber. According to our results, a 25rpm rotation (i) enhances an adequate mixing of the cell carriers, avoiding sedimentation and excessive packing, also maintaining a quite homogeneous distribution of the suspended beads and (ii) imparts a proper cellular O-2 supply, providing cells close to a normoxia condition. The bioreactor working conditions derived from the numerical analysis allowed the attainment of in vitro long-term cell viability maintenance, supporting efficient large-scale generation of ESC-derived cardiomyocytes (ESC-DCs) through a chemical-based conditioning bioprocess. In conclusion, we demonstrated the feasibility of using CFD-based tools, as a reliable and cost-effective strategy to assist the design of a 3D cardiogenic bioprocess.