Guzniczak Ewa, Jimenez Melanie, Irwin Matthew, Otto Oliver, Willoughby Nicholas, Bridle Helen
Institute of Biological Chemistry, Biophysics and Bioengineering, School of Engineering and Physical Science, Heriot-Watt University, Edinburgh Campus, Edinburgh EH14 4AS, United Kingdom.
School of Engineering, Biomedical Engineering Division, University of Glasgow, Glasgow G12 8LT, United Kingdom.
Biomicrofluidics. 2018 Aug 22;12(4):044118. doi: 10.1063/1.5040316. eCollection 2018 Jul.
Advances in cellular therapies have led to the development of new approaches for cell product purification and formulation, e.g., utilizing cell endogenous properties such as size and deformability as a basis for separation from potentially harmful undesirable by-products. However, commonly used additives such as Pluronic F-68 and other poloxamer macromolecules can change the mechanical properties of cells and consequently alter their processing. In this paper, we quantified the short-term effect of Pluronic F-68 on the mechanotype of three different cell types (Jurkat cells, red blood cells, and human embryonic kidney cells) using real-time deformability cytometry. The impact of the additive concentration was assessed in terms of cell size and deformability. We observed that cells respond progressively to the presence of Pluronic F-68 within first 3 h of incubation and become significantly stiffer (p-value < 0.001) in comparison to a serum-free control and a control containing serum. We also observed that the short-term response manifested as cell stiffening is true (p-value < 0.001) for the concentration reaching 1% (w/v) of the poloxamer additive in tested buffers. Additionally, using flow cytometry, we assessed that changes in cell deformability triggered by addition of Pluronic F-68 are not accompanied by size or viability alterations.
细胞疗法的进展促使了细胞产品纯化和制剂新方法的发展,例如,利用细胞的内源性特性(如大小和可变形性)作为从潜在有害的不良副产物中分离的基础。然而,常用的添加剂如普朗尼克F-68和其他泊洛沙姆大分子会改变细胞的机械性能,从而改变其处理过程。在本文中,我们使用实时可变形性细胞术量化了普朗尼克F-68对三种不同细胞类型(Jurkat细胞、红细胞和人胚肾细胞)机械类型的短期影响。从细胞大小和可变形性方面评估了添加剂浓度的影响。我们观察到,细胞在孵育的最初3小时内对普朗尼克F-68的存在有逐渐反应,与无血清对照和含血清对照相比,细胞变得明显更硬(p值<0.001)。我们还观察到,对于测试缓冲液中泊洛沙姆添加剂浓度达到1%(w/v)的情况,表现为细胞变硬的短期反应是真实的(p值<0.001)。此外,使用流式细胞术,我们评估了添加普朗尼克F-68引发的细胞可变形性变化并未伴随着大小或活力的改变。