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新型生物工艺用于临床所需造血细胞的规模化生产的性能评估。

Performance evaluation of a novel conceptual bioprocess for clinically-required mass production of hematopoietic cells.

机构信息

Chemical Engineering Faculty, Sahand University of Technology, 51335-1996, Tabriz, Iran.

Stem Cell and Tissue Engineering Research Laboratory, Sahand University of Technology, 51335-1996, Tabriz, Iran.

出版信息

Biotechnol Lett. 2021 May;43(5):959-966. doi: 10.1007/s10529-020-03062-1. Epub 2021 Feb 8.

Abstract

OBJECTIVE

The novel engineered bioprocess, which was designed and modeled to provide the clinically relevant cell numbers for different therapies in our previous work (Kaleybar et al. Food Bioprod Process 122:254-268, https://doi.org/10.1016/j.fbp.2020.04.012 , 2020), was evaluated by using U937 as hematopoietic model cells.

RESULTS

The culture system showed a 30-fold expansion of U937 cells in one-step during a 10-day culture period. The cell growth profile, the substrate and oxygen consumptions, and byproduct formations were all in agreement with the model predications during 7 days. The cell proliferation decrease after 7 days was attributed to optional oxygen limiting condition in the last days of culture. The bioreactor culture system revealed also a slight enhancement of lactate dehydrogenase (LDH) production as compared to the 2D conventional culture system, indicating the low impact of shear stress on cellular damage in the dynamic system.

CONCLUSIONS

The results demonstrated that the conceptual bioprocess for suspended stem cell production has a great potential in practice although additional experiments are required to improve the system.

摘要

目的

在我们之前的工作中(Kaleybar 等人,《食品生物加工》122:254-268,https://doi.org/10.1016/j.fbp.2020.04.012,2020),设计并建模了一种新的工程生物工艺,旨在为不同疗法提供临床相关数量的细胞,本研究使用 U937 作为造血模型细胞对其进行了评估。

结果

在 10 天的培养期内,该培养系统使 U937 细胞在一步骤中扩增了 30 倍。细胞生长曲线、底物和氧气消耗以及副产物形成在第 7 天内均与模型预测相符。第 7 天后细胞增殖减少归因于培养后期可选的氧气限制条件。与二维常规培养系统相比,生物反应器培养系统还显示出乳酸脱氢酶(LDH)产量略有增加,表明在动态系统中剪切力对细胞损伤的影响较小。

结论

尽管需要进一步的实验来改进该系统,但这些结果表明,悬浮干细胞生产的概念性生物工艺具有很大的实践潜力。

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