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了解用于人间质基质细胞的生物活性涂层材料的影响及其对制造的意义。

Understanding the impact of bioactive coating materials for human mesenchymal stromal cells and implications for manufacturing.

机构信息

Department of Biochemical Engineering, Advanced Centre for Biochemical Engineering, University College London, Gower Street, London, WC1E 6BT, UK.

Applied Research & Technology Scouting R&D, West Pharmaceutical Services, Inc., Exton, PA, USA.

出版信息

Biotechnol Lett. 2023 Aug;45(8):1013-1027. doi: 10.1007/s10529-023-03369-9. Epub 2023 May 25.

Abstract

Bioactive materials interact with cells and modulate their characteristics which enable the generation of cell-based products with desired specifications. However, their evaluation and impact are often overlooked when establishing a cell therapy manufacturing process. In this study, we investigated the role of different surfaces for tissue culture including, untreated polystyrene surface, uncoated Cyclic Olefin Polymer (COP) and COP coated with collagen and recombinant fibronectin. It was observed that human mesenchymal stromal cells (hMSCs) expanded on COP-coated plates with different bioactive materials resulted in improved cell growth kinetics compared to traditional polystyrene plates and non-coated COP plates. The doubling time obtained was 2.78 and 3.02 days for hMSC seeded in COP plates coated with collagen type I and recombinant fibronectin respectively, and 4.64 days for cells plated in standard polystyrene treated plates. Metabolite analysis reinforced the findings of the growth kinetic studies, specifically that cells cultured on COP plates coated with collagen I and fibronectin exhibited improved growth as evidenced by a higher lactate production rate (9.38 × 10 and 9.67 × 10 pmol/cell/day, respectively) compared to cells from the polystyrene group (5.86 × 10 pmol/cell/day). This study demonstrated that COP is an effective alternative to polystyrene-treated plates when coated with bioactive materials such as collagen and fibronectin, however COP-treated plates without additional coatings were found not to be sufficient to support cell growth. These findings demonstrate the key role biomaterials play in the cell manufacturing process and the importance of optimising this selection.

摘要

生物活性材料与细胞相互作用并调节其特性,从而能够生成具有所需特性的基于细胞的产品。然而,在建立细胞治疗制造工艺时,往往会忽略对其的评估和影响。在本研究中,我们研究了包括未经处理的聚苯乙烯表面、未涂覆的环烯烃聚合物 (COP) 以及涂覆有胶原蛋白和重组纤维连接蛋白的 COP 在内的不同组织培养表面在细胞治疗制造中的作用。结果表明,与传统的聚苯乙烯板和未涂覆的 COP 板相比,在涂覆有不同生物活性材料的 COP 板上扩展的人间充质基质细胞 (hMSC) 导致细胞生长动力学得到改善。接种在涂覆有胶原蛋白 I 和重组纤维连接蛋白的 COP 板上的 hMSC 的倍增时间分别为 2.78 和 3.02 天,而接种在标准聚苯乙烯处理板上的细胞的倍增时间为 4.64 天。代谢物分析加强了生长动力学研究的结果,特别是在涂覆有胶原蛋白 I 和纤维连接蛋白的 COP 板上培养的细胞表现出更好的生长,这表现为更高的乳酸产生率(分别为 9.38×10 和 9.67×10 pmol/细胞/天)与聚苯乙烯组的细胞相比(5.86×10 pmol/细胞/天)。这项研究表明,当 COP 板涂覆有胶原蛋白和纤维连接蛋白等生物活性材料时,COP 是替代聚苯乙烯处理板的有效方法,然而,未涂覆额外涂层的 COP 板被发现不足以支持细胞生长。这些发现表明生物材料在细胞制造过程中起着关键作用,并且优化这种选择非常重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05fe/10276101/b55c402dc32b/10529_2023_3369_Fig1_HTML.jpg

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