Scale-up of an intensified bioprocess for the expansion of bovine adipose-derived stem cells (bASCs) in stirred tank bioreactors
Scale-up of an intensified bioprocess for the expansion of bovine adipose-derived stem cells (bASCs) in stirred tank bioreactors
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DOI：
10.1002/bit.27842
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发表时间：
2021-06-02
影响因子：
3.8
通讯作者：
Wall, Ivan
中科院分区：
文献类型：
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作者：
Hanga, Mariana Petronela;de la Raga, Fritz Anthony;Wall, Ivan
人工培植肉类是一个新兴领域，旨在建立在体外环境中生产供人类食用的动物组织，消除饲养和屠宰动物获取肉类的需要。为了实现这一点，需要在生物反应器中扩大初级细胞，以达到所需的高细胞数量。这项研究的目的是开发一种可扩展的、基于微载体的强化生物过程，用于牛脂肪来源干细胞的扩增，作为脂肪和肌肉组织的前体。强化生物工艺的开发最初是在不同大小的旋转烧瓶中进行的，然后转化为完全受控的公升规模台式生物反应器。生物过程强化是通过利用先前证明的珠对珠转移现象并通过微载体和介质的组合添加来实现的，从而使生物反应器中的现有表面积和工作体积增加了一倍。选择添加的最佳时间点是促进细胞扩张的关键。与基线(**p<；.005)相比，强化生物过程的升规模显著增加了114.19+/-1.07倍。扩增前后对细胞质量进行评价，发现细胞保持其表型和分化能力。
Cultivated meat is an emerging field, aiming to establish the production of animal tissue for human consumption in an in vitro environment, eliminating the need to raise and slaughter animals for their meat. To realise this, the expansion of primary cells in a bioreactor is needed to achieve the high cell numbers required. The aim of this study was to develop a scalable, microcarrier based, intensified bioprocess for the expansion of bovine adipose-derived stem cells as precursors of fat and muscle tissue. The intensified bioprocess development was carried out initially in spinner flasks of different sizes and then translated to fully controlled litre scale benchtop bioreactors. Bioprocess intensification was achieved by utilising the previously demonstrated bead-to-bead transfer phenomenon and through the combined addition of microcarrier and medium to double the existing surface area and working volume in the bioreactor. Choosing the optimal time point for the additions was critical in enhancing the cell expansion. A significant fold increase of 114.19 +/- 1.07 was obtained at the litre scale in the intensified bioprocess compared to the baseline (**p < .005). The quality of the cells was evaluated pre- and post-expansion and the cells were found to maintain their phenotype and differentiation capacity.