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Using magnetic nanoparticles for gene transfer to neural stem cells: stem cell propagation method influences outcomes

Pickard, Mark R.
Adams, Christopher F.
Barraud, Perrine
Chari, Divya M.
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Publication Date
2015-04-24
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Abstract
Genetically engineered neural stem cell (NSC) transplants offer a key strategy to augment neural repair by releasing therapeutic biomolecules into injury sites. Genetic modification of NSCs is heavily reliant on viral vectors but cytotoxic effects have prompted development of non-viral alternatives, such as magnetic nanoparticle (MNPs). NSCs are propagated in laboratories as either 3-D suspension "neurospheres" or 2-D adherent "monolayers". MNPs deployed with oscillating magnetic fields ("magnetofection technology") mediate effective gene transfer to neurospheres but the efficacy of this approach for monolayers is unknown. It is important to address this issue as oscillating magnetic fields dramatically enhance MNP-based transfection in transplant cells (e.g., astrocytes and oligodendrocyte precursors) propagated as monolayers. We report for the first time that oscillating magnetic fields enhanced MNP-based transfection with reporter and functional (basic fibroblast growth factor; FGF2) genes in monolayer cultures yielding high transfection versus neurospheres. Transfected NSCs showed high viability and could re-form neurospheres, which is important as neurospheres yield higher post-transplantation viability versus monolayer cells. Our results demonstrate that the combination of oscillating magnetic fields and a monolayer format yields the highest efficacy for MNP-mediated gene transfer to NSCs, offering a viable non-viral alternative for genetic modification of this important neural cell transplant population.
Citation
Pickard, M. R., Adams, C. F., Barraud, P., & Chari, D. M. (2015). Using magnetic nanoparticles for gene transfer to neural stem cells: stem cell propagation method influences outcomes. Journal of Functional Biomaterials, 6(2), 259-76. http://dx.doi.org/10.3390/jfb6020259
Publisher
MDPI
Journal
Journal of Functional Biomaterials
Research Unit
DOI
10.3390/jfb6020259
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PubMed Central ID
Type
Article
Language
en
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ISSN
2079-4983
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Sponsors
Biotechnology and Biological Sciences Research Council, UK; Doctoral Training Centre in Regenerative Medicine, Engineering and Physical Sciences Research Council, UK
Additional Links
http://www.mdpi.com/2079-4983/6/2/259