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首页> 外文期刊>Journal of tissue engineering and regenerative medicine >The productivity limit of manufacturing blood cell therapy in scalable stirred bioreactors
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The productivity limit of manufacturing blood cell therapy in scalable stirred bioreactors

机译：可伸缩搅拌生物反应器中制造血细胞治疗的生产率极限

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Manufacture of red blood cells (RBCs) from progenitors has been proposed as a method to reduce reliance on donors. Such a process would need to be extremely efficient for economic viability given a relatively low value product and high (2x10(12)) cell dose. Therefore, the aim of these studies was to define the productivity of an industry standard stirred-tank bioreactor and determine engineering limitations of commercial red blood cells production. Cord blood derived CD34+ cells were cultured under erythroid differentiation conditions in a stirred micro-bioreactor (Ambr (TM)). Enucleated cells of 80% purity could be created under optimal physical conditions: pH7.5, 50% oxygen, without gas-sparging (which damaged cells) and with mechanical agitation (which directly increased enucleation). O-2 consumption was low (similar to 5x10(-8) mu g/cell.h) theoretically enabling erythroblast densities in excess of 5x10(8)/ml in commercial bioreactors and sub-10 l/unit production volumes. The bioreactor process achieved a 24% and 42% reduction in media volume and culture time, respectively, relative to unoptimized flask processing. However, media exchange limited productivity to 1 unit of erythroblasts per 500 l of media. Systematic replacement of media constituents, as well as screening for inhibitory levels of ammonia, lactate and key cytokines did not identify a reason for this limitation. We conclude that the properties of erythroblasts are such that the conventional constraints on cell manufacturing efficiency, such as mass transfer and metabolic demand, should not prevent high intensity production; furthermore, this could be achieved in industry standard equipment. However, identification and removal of an inhibitory mediator is required to enable these economies to be realized. Copyright (c) 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd.
机译：已经提出了来自祖细胞的红细胞（RBC）作为减少依赖捐献者的方法。在给予相对低的价值产品和高（2×10（12））细胞剂量的情况下，这种过程需要极其有效的经济活力。因此，这些研究的目的是定义行业标准搅拌罐生物反应器的生产率，并确定商业红细胞产生的工程限制。在搅拌的微生物反应器（AMBR（TM）中的红细胞分化条件下培养脐带血衍生的CD34 +细胞。可以在最佳物理条件下产生80％纯度的纯纯度：pH7.5，50％氧气，无烟雾喷射（受损细胞）和机械搅拌（直接增加的enucleation）。 O-2消耗量低（类似于5x10（-8）mu g / cell.h），理论上使得在商业生物反应器和亚10L /单位产生体积中，过量的红细胞密度超过5×10（8）/ mL。相对于未优化的烧瓶加工，生物反应器方法分别达到介质体积和培养时间的24％和42％。然而，媒体将生产力有限为每500升培养基的1单位红细胞性。系统替代培养基成分，以及筛查氨氨症，乳酸和关键细胞因子的筛选不确定这种限制的原因。我们得出结论，红细胞细胞的性质使得对细胞制造效率的常规约束，例如传质和代谢需求，不应预防高强度产生;此外，这可以在工业标准设备中实现。然而，需要识别和去除抑制介质，以使这些经济能够实现。版权所有（C）2016作者作者：John Wiley＆Sons Ltd.出版的组织工程和再生医学杂志

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