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http://hdl.handle.net/2445/202107
Title: | Artificial extracellular matrix scaffolds of mobile molecules enhance maturation of human stem cell-derived neurons |
Author: | Álvarez, Zaida Ortega, J. Alberto Sato, Kohei Sasselli, Ivan R. Kolberg Edelbrock, Alexandra N. Qiu, Ruomeng Marshall, Kelly A. Nguyen, Thao Phuong Smith, Cara S. Quinlan, Katharina A. Papakis, Vasileios Syrgiannis, Zois Sather, Nicholas A. Musumeci, Chiara Engel, Elisabeth Stupp, Samuel I. Kiskinis, Evangelos |
Keywords: | Neurones Cèl·lules mare Proteòmica Enginyeria biomèdica Neurons Stem cells Proteomics Biomedical engineering |
Issue Date: | 12-Jan-2023 |
Publisher: | Elsevier B.V. |
Abstract: | 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 β1-integrin pathway activation, reduced aggregation, increased arborization, and matured electrophysiological activity of neurons. Our work highlights the importance of designing biomimetic ECMs to study the development, function, and dysfunction of human neurons. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1016/j.stem.2022.12.010 |
It is part of: | Cell Stem Cell, 2023, vol. 30, num. 2, p. 219-238.e14 |
URI: | http://hdl.handle.net/2445/202107 |
Related resource: | https://doi.org/10.1016/j.stem.2022.12.010 |
ISSN: | 1934-5909 |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) |
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