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Nanoengineering neural stem cells on biomimetic substrates using magnetofection technology.

Adams, CF; Dickson, AW; Kuiper, J-H; Chari, DM

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Authors

AW Dickson



Abstract

Tissue engineering studies are witnessing a major paradigm shift to cell culture on biomimetic materials that replicate native tissue features from which the cells are derived. Few studies have been performed in this regard for neural cells, particularly in nanomedicine. For example, platforms such as magnetic nanoparticles (MNPs) have proven efficient as multifunctional tools for cell tracking and genetic engineering of neural transplant populations. However, as far as we are aware, all current studies have been conducted using neural cells propagated on non-neuromimetic substrates that fail to represent the mechano-elastic properties of brain and spinal cord microenvironments. Accordingly, it can be predicted that such data is of less translational and physiological relevance than that derived from cells grown in neuromimetic environments. Therefore, we have performed the first test of magnetofection technology (enhancing MNP delivery using applied magnetic fields with significant potential for therapeutic application) and its utility in genetically engineering neural stem cells (NSCs; a population of high clinical relevance) propagated in biomimetic hydrogels. We demonstrate magnetic field application safely enhances MNP mediated transfection of NSCs grown as 3D spheroid structures in collagen which more closely replicates the intrinsic mechanical and structural properties of neural tissue than routinely used hard substrates. Further, as it is well known that MNP uptake is mediated by endocytosis we also investigated NSC membrane activity grown on both soft and hard substrates. Using high resolution scanning electron microscopy we were able to prove that NSCs display lower levels of membrane activity on soft substrates compared to hard, a finding which could have particular impact on MNP mediated engineering strategies of cells propagated in physiologically relevant systems.

Journal Article Type Article
Acceptance Date Sep 27, 2016
Publication Date Sep 28, 2016
Publicly Available Date Mar 28, 2024
Journal Nanoscale
Print ISSN 2040-3364
Electronic ISSN 2040-3372
Publisher Royal Society of Chemistry
Volume 8
Pages 17869-17880
DOI https://doi.org/10.1039/c6nr05244d
Keywords Magnetic nanoparticle, transfection, neural stem cell, biomimetic hydrogel, electron microscopy, membrane activity
Publisher URL https://www.ncbi.nlm.nih.gov/pubmed/27714076

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