Using computational fluid dynamics (CFD) modeling to understand murine embryonic stem cell aggregate size and pluripotency distributions in stirred suspension bioreactors
Using computational fluid dynamics (CFD) modeling to understand murine embryonic stem cell aggregate size and pluripotency distributions in stirred suspension bioreactors
复制标题
DOI：
10.1016/j.jbiotec.2019.08.002
复制
发表时间：
2019-10-10
影响因子：
4.1
通讯作者：
Kallos, Michael S.
中科院分区：
文献类型：
--
作者：
Borys, Breanna S.;Le, An;Kallos, Michael S.
计算流体动力学（CFD）建模可以应用于理解搅拌悬浮生物反应器中的流体动力学，这反过来又会影响细胞活力，增殖，多能性和分化。在这项研究中，我们开发了一个计算流体动力学模型，以确定平均剪切速率和湍流涡流对小鼠胚胎干细胞聚集体的形成和生长的影响。我们发现平均涡流大小和聚集体大小之间的相关性，这取决于生物反应器搅拌速率。通过将这些计算变量和生物变量相关联，CFD建模可以预测在搅拌悬浮生物反应器中生长胚胎干细胞聚集体的最佳搅拌速率。为了检查流体动力学对多能性的影响，测试在各种搅拌速率下在生物反应器中培养的mESC的SSEA-1、Sox-2和Nanog表达。细胞保持至少95%的阳性表达，不同生物反应器条件之间的强度分布模式无变化。这表明多能性标志物表达的平均水平与流体动力学特征和所得聚集体尺寸分布的变化无关。这里的发现可以进一步扩展到在搅拌悬浮生物反应器中作为聚集体生长的其他细胞类型，并提供实现细胞疗法所需的重要见解。
Computational fluid dynamics (CFD) modeling can be applied to understand hydrodynamics in stirred suspension bioreactors, which can in turn affect cell viability, proliferation, pluripotency and differentiation. In this study, we developed a CFD model to determine the effects of average shear rates and turbulent eddies on the formation and growth of murine embryonic stem cell aggregates. We found a correlation between average eddy size and aggregate size, which depended on bioreactor agitation rates. By relating these computational and biological variables, CFD modeling can predict optimal agitation rates to grow embryonic stem cell aggregates in stirred suspension bioreactors. To examine the effect of hydrodynamics on pluripotency, mESCs cultured in bioreactors under various agitation rates were tested for SSEA-1, Sox-2, and Nanog expression. Cells maintained a minimum of 95% positive expression with no change in the intensity distribution pattern between the different bioreactor conditions. This indicates that the average level of pluripotency marker expression is independent of changes in the hydrodynamic profile and resulting aggregate size distribution. The findings here can be further extended to other cell types that grow as aggregates in stirred suspension bioreactors and offer important insights necessary to realize cell therapies.