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

被引:61
作者
Alvarez, Zaida [1 ,7 ,9 ]
Ortega, J. Alberto [2 ,10 ]
Sato, Kohei [1 ,3 ]
Sasselli, Ivan R. [1 ,3 ,11 ]
Kolberg-Edelbrock, Alexandra N. [1 ,4 ]
Qiu, Ruomeng [1 ,3 ]
Marshall, Kelly A. [2 ]
Nguyen, Thao Phuong [2 ,4 ]
Smith, Cara S. [1 ,4 ]
Quinlan, Katharina A. [5 ]
Papakis, Vasileios [2 ]
Syrgiannis, Zois [1 ,3 ]
Sather, Nicholas A. [1 ]
Musumeci, Chiara [6 ]
Engel, Elisabeth [9 ]
Stupp, Samuel I. [1 ,3 ,4 ,7 ]
Kiskinis, Evangelos [1 ,2 ,8 ]
机构
[1] Northwestern Univ, Simpson Querrey Inst BioNanotechnol, Chicago, IL 60611 USA
[2] Northwestern Univ, Feinberg Sch Med, Ken & Ruth Davee Dept Neurol, Chicago, IL 60611 USA
[3] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA
[4] Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA
[5] Univ Rhode Isl, Coll Pharm, Dept Biomed & Pharmaceut Sci, Kingston, RI 02881 USA
[6] Northwestern Univ, Dept Mat Sci & Engn, Evanston, IL 60208 USA
[7] Northwestern Univ, Dept Med, Chicago, IL 60611 USA
[8] Northwestern Univ, Feinberg Sch Med, Dept Neurosci, Chicago, IL 60611 USA
[9] Inst Bioengn Catalonia IBEC, Biomat Regenerat Therapies, Barcelona 08028, Spain
[10] Univ Barcelona, Fac Med & Hlth Sci, Dept Pathol & Expt Therapeut, LHospitalet Llobregat, Barcelona 08907, Spain
[11] Basque Res & Technol Alliance BRTA, Ctr Cooperat Res Biomat CIC biomaGUNE, Donostia San Sebastian 20014, Spain
基金
美国国家卫生研究院;
关键词
COARSE-GRAINED MODEL; SPINAL-CORD; SUPRAMOLECULAR MATERIALS; PEPTIDE AMPHIPHILES; STATISTICAL-MODEL; FORCE-FIELD; MIGRATION; LAMININ; NANOSTRUCTURES; DIFFERENTIATION;
D O I
10.1016/j.stem.2022.12.010
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Human induced pluripotent stem cell (hiPSC) technologies offer a unique resource for modeling neurological diseases. However, iPSC models are fraught with technical limitations including abnormal aggregation and inefficient maturation of differentiated neurons. These problems are in part due to the absence of synergistic cues of the native extracellular matrix (ECM). We report on the use of three artificial ECMs based on peptide amphiphile (PA) supramolecular nanofibers. All nanofibers display the laminin-derived IKVAV signal on their surface but differ in the nature of their non-bioactive domains. We find that nanofibers with greater intensity of internal supramolecular motion have enhanced bioactivity toward hiPSC-derived motor and cortical neurons. Proteomic, biochemical, and functional assays reveal that highly mobile PA scaffolds caused enhanced b1-integrin pathway activation, reduced aggregation, increased arborization, and matured electrophysiolog-ical activity of neurons. Our work highlights the importance of designing biomimetic ECMs to study the devel-opment, function, and dysfunction of human neurons.
引用
收藏
页码:219 / +
页数:35
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