美国西北大学Evangelos Kiskinis和Samuel I. Stupp共同合作，近期取得重要工作进展。他们研究发现移动分子的人工细胞外基质支架增强人类干细胞来源神经元的成熟。相关研究成果2023年1月12日在线发表于《细胞—干细胞》杂志上。

据介绍，人类诱导多能干细胞（hiPSC）技术为神经系统疾病建模提供了独特的资源。然而，iPSC模型充满了技术限制，包括分化神经元的异常聚集和低效成熟。这些问题部分是由于缺乏天然细胞外基质（ECM）导致的。

研究人员报告了基于多肽双亲（PA）超分子纳米纤维的三种人工ECM的使用。所有纳米纤维在其表面显示层粘连蛋白来源的IKVAV信号，但在其非生物活性域的性质上有所不同。研究人员发现，具有更大强度的内部超分子运动的纳米纤维增强了对hiPSC来源的运动神经元和皮层神经元的生物活性。蛋白质组学、生物化学和功能分析表明，高流动性的PA支架可增强β1-整合素通路的激活、减少聚集、增加树突化和神经元的成熟电生理活性。

总之，这一工作强调了设计仿生ECM以研究人类神经元的发育、功能和功能障碍的重要性。

附：英文原文

Title: Artificial extracellular matrix scaffolds of mobile molecules enhance maturation of human stem cell-derived neurons

Author: Zaida álvarez, J. Alberto Ortega, Kohei Sato, Ivan R. Sasselli, Alexandra N. Kolberg-Edelbrock, Ruomeng Qiu, Kelly A. Marshall, Thao Phuong Nguyen, Cara S. Smith, Katharina A. Quinlan, Vasileios Papakis, Zois Syrgiannis, Nicholas A. Sather, Chiara Musumeci, Elisabeth Engel, Samuel I. Stupp, Evangelos Kiskinis

Issue&Volume: 2023-01-12

Abstract: Human induced pluripotent stem cell (hiPSC) technologies offer a unique resource formodeling neurological diseases. However, iPSC models are fraught with technical limitationsincluding abnormal aggregation and inefficient maturation of differentiated neurons.These problems are in part due to the absence of synergistic cues of the native extracellularmatrix (ECM). We report on the use of three artificial ECMs based on peptide amphiphile(PA) supramolecular nanofibers. All nanofibers display the laminin-derived IKVAV signalon their surface but differ in the nature of their non-bioactive domains. We findthat nanofibers with greater intensity of internal supramolecular motion have enhancedbioactivity toward hiPSC-derived motor and cortical neurons. Proteomic, biochemical,and functional assays reveal that highly mobile PA scaffolds caused enhanced β1-integrinpathway activation, reduced aggregation, increased arborization, and matured electrophysiologicalactivity of neurons. Our work highlights the importance of designing biomimetic ECMsto study the development, function, and dysfunction of human neurons.

DOI: 10.1016/j.stem.2022.12.010

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00494-5