Hybrid Systems Lab, NanoScience Technology Center, University of Central Florida, 12424 Research Parkway, Suite 400, Orlando, Florida 32826, United States.
ACS Chem Neurosci. 2020 Apr 1;11(7):1085-1092. doi: 10.1021/acschemneuro.0c00055. Epub 2020 Mar 19.
Human-based "body-on-a-chip" technology provides powerful platforms in developing models for drug evaluation and disease evaluations in phenotypic models. Induced pluripotent stem cells (iPSCs) are ideal cell sources for generating different cell types for these functional systems and recapitulation of the neuromuscular reflex arc would allow for the study of patient specific neuromuscular diseases. Regarding relevant afferent (intrafusal fibers, sensory neurons) and efferent (extrafusal fibers, motoneurons) cells, differentiation of intrafusal fiber from human iPSCs has not been established. This work demonstrates a protocol for inducing an enrichment of intrafusal bag fibers from iPSCs using morphological analysis and immunocytochemistry. Phosphorylation of the ErbB2 receptors and S46 staining indicated a 3-fold increase of total intrafusal fibers further confirming the efficiency of the protocol. Integration of induced intrafusal fibers would enable more accurate reflex arc models and application of this protocol on patient iPSCs would allow for patient-specific disease modeling.
基于人体的“芯片上的器官”技术为药物评价和表型模型中的疾病评估开发模型提供了强大的平台。诱导多能干细胞（iPSCs）是为这些功能性系统生成不同细胞类型和再现神经肌肉反射弧的理想细胞来源，这将允许研究特定于患者的神经肌肉疾病。关于相关的传入（内收肌纤维，感觉神经元）和传出（外展肌纤维，运动神经元）细胞，从人 iPSCs 中分化内收肌纤维尚未建立。本工作展示了一种使用形态分析和免疫细胞化学从 iPSCs 中诱导内收肌纤维富集的方案。ErbB2 受体的磷酸化和 S46 染色表明总内收肌纤维增加了 3 倍，进一步证实了该方案的效率。诱导的内收肌纤维的整合将使反射弧模型更加准确，并且将该方案应用于患者的 iPSCs 将允许进行患者特异性疾病建模。
