Khodadadei Fatemeh, Liu Allen P, Harris Carolyn A
Dept. of Chemical Engineering and Materials Science, Wayne State University, Detroit, MI, USA.
Dept. of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA.
Commun Biol. 2021 Mar 23;4(1):387. doi: 10.1038/s42003-021-01888-7.
It has been hypothesized that physiological shear forces acting on medical devices implanted in the brain significantly accelerate the rate to device failure in patients with chronically indwelling neuroprosthetics. In hydrocephalus shunt devices, shear forces arise from cerebrospinal fluid flow. The shunt's unacceptably high failure rate is mostly due to obstruction with adherent inflammatory cells. Astrocytes are the dominant cell type bound directly to obstructing shunts, rapidly manipulating their activation via shear stress-dependent cytokine secretion. Here we developed a total internal reflection fluorescence microscopy combined with a microfluidic shear device chip (MSDC) for quantitative analysis and direct spatial-temporal mapping of secreted cytokines at the single-cell level under physiological shear stress to identify the root cause for shunt failure. Real-time secretion imaging at 1-min time intervals enabled successful detection of a significant increase of astrocyte IL-6 cytokine secretion under shear stress greater than 0.5 dyne/cm, validating our hypothesis and highlighting the importance of reducing shear stress activation of cells.
据推测，作用于植入大脑的医疗设备上的生理剪切力会显著加速长期植入神经假体患者的设备故障率。在脑积水分流装置中，剪切力源于脑脊液流动。分流装置高得令人无法接受的故障率主要是由于被粘附的炎性细胞阻塞。星形胶质细胞是直接与阻塞性分流装置结合的主要细胞类型，通过剪切应力依赖性细胞因子分泌迅速调节其激活。在这里，我们开发了一种全内反射荧光显微镜与微流控剪切装置芯片（MSDC）相结合的技术，用于在生理剪切应力下对单细胞水平分泌的细胞因子进行定量分析和直接的时空映射，以确定分流失败的根本原因。以1分钟的时间间隔进行实时分泌成像，成功检测到在剪切应力大于0.5达因/平方厘米时星形胶质细胞IL-6细胞因子分泌显著增加，验证了我们的假设，并突出了降低细胞剪切应力激活的重要性。
