Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Department of Electrical Engineering, Stanford University, Stanford, CA, USA.
Sci Rep. 2019 Dec 20;9(1):19565. doi: 10.1038/s41598-019-56021-w.
Human induced pluripotent stem cell-derived neural progenitor cells (hNPCs) are a promising cell source for stem cell transplantation to treat neurological diseases such as stroke and peripheral nerve injuries. However, there have been limited studies investigating how the dimensionality of the physical and electrical microenvironment affects hNPC function. In this study, we report the fabrication of two- and three-dimensional (2D and 3D respectively) constructs composed of a conductive polymer to compare the effect of electrical stimulation of hydrogel-immobilized hNPCs. The physical dimension (2D vs 3D) of stimulating platforms alone changed the hNPCs gene expression related to cell proliferation and metabolic pathways. The addition of electrical stimulation was critical in upregulating gene expression of neurotrophic factors that are important in regulating cell survival, synaptic remodeling, and nerve regeneration. This study demonstrates that the applied electrical field controls hNPC properties depending on the physical nature of stimulating platforms and cellular metabolic states. The ability to control hNPC functions can be beneficial in understanding mechanistic changes related to electrical modulation and devising novel treatment methods for neurological diseases.
人诱导多能干细胞衍生的神经祖细胞（hNPCs）是一种很有前途的干细胞移植来源，可用于治疗中风和周围神经损伤等神经系统疾病。然而，目前关于物理和电气微环境的维度如何影响 hNPC 功能的研究还很有限。在这项研究中，我们报告了由导电聚合物组成的二维和三维（分别为 2D 和 3D）构建体的制造，以比较水凝胶固定的 hNPCs 的电刺激效果。刺激平台的物理维度（2D 与 3D）单独改变了与细胞增殖和代谢途径相关的 hNPCs 基因表达。电刺激的加入对于上调神经营养因子的基因表达至关重要，这些因子在调节细胞存活、突触重塑和神经再生方面起着重要作用。这项研究表明，施加的电场会根据刺激平台的物理性质和细胞代谢状态来控制 hNPC 的特性。控制 hNPC 功能的能力有助于理解与电调节相关的机制变化，并为神经系统疾病设计新的治疗方法。
