Using Magnetic Nanoparticles for Gene Transfer to Neural Stem Cells: Stem Cell Propagation Method Influences Outcomes
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,...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2015-04-01
|
| Series: | Journal of Functional Biomaterials |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2079-4983/6/2/259 |
| _version_ | 1818015342762393600 |
|---|---|
| author | Mark R. Pickard Christopher F. Adams Perrine Barraud Divya M. Chari |
| author_facet | Mark R. Pickard Christopher F. Adams Perrine Barraud Divya M. Chari |
| author_sort | Mark R. Pickard |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T06:56:34Z |
| format | Article |
| id | doaj.art-e0aa69e4dfa743108b95dbddefe533b6 |
| institution | Directory Open Access Journal |
| issn | 2079-4983 |
| language | English |
| last_indexed | 2024-04-14T06:56:34Z |
| publishDate | 2015-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Functional Biomaterials |
| spelling | doaj.art-e0aa69e4dfa743108b95dbddefe533b62022-12-22T02:06:53ZengMDPI AGJournal of Functional Biomaterials2079-49832015-04-016225927610.3390/jfb6020259jfb6020259Using Magnetic Nanoparticles for Gene Transfer to Neural Stem Cells: Stem Cell Propagation Method Influences OutcomesMark R. Pickard0Christopher F. Adams1Perrine Barraud2Divya M. Chari3Cellular and Neural Engineering Group, Institute for Science and Technology in Medicine, Keele University, Keele, Staffordshire ST5 5BG, UKCellular and Neural Engineering Group, Institute for Science and Technology in Medicine, Keele University, Keele, Staffordshire ST5 5BG, UKDepartment of Physiology, Development and Neuroscience, University of Cambridge, Anatomy Building, Downing Street, Cambridge CB2 3DY, UKCellular and Neural Engineering Group, Institute for Science and Technology in Medicine, Keele University, Keele, Staffordshire ST5 5BG, UKGenetically 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.http://www.mdpi.com/2079-4983/6/2/259nanoparticlemagnetofectionneural cellstem celltransplantationgenetic engineering |
| spellingShingle | Mark R. Pickard Christopher F. Adams Perrine Barraud Divya M. Chari Using Magnetic Nanoparticles for Gene Transfer to Neural Stem Cells: Stem Cell Propagation Method Influences Outcomes Journal of Functional Biomaterials nanoparticle magnetofection neural cell stem cell transplantation genetic engineering |
| title | Using Magnetic Nanoparticles for Gene Transfer to Neural Stem Cells: Stem Cell Propagation Method Influences Outcomes |
| title_full | Using Magnetic Nanoparticles for Gene Transfer to Neural Stem Cells: Stem Cell Propagation Method Influences Outcomes |
| title_fullStr | Using Magnetic Nanoparticles for Gene Transfer to Neural Stem Cells: Stem Cell Propagation Method Influences Outcomes |
| title_full_unstemmed | Using Magnetic Nanoparticles for Gene Transfer to Neural Stem Cells: Stem Cell Propagation Method Influences Outcomes |
| title_short | Using Magnetic Nanoparticles for Gene Transfer to Neural Stem Cells: Stem Cell Propagation Method Influences Outcomes |
| title_sort | using magnetic nanoparticles for gene transfer to neural stem cells stem cell propagation method influences outcomes |
| topic | nanoparticle magnetofection neural cell stem cell transplantation genetic engineering |
| url | http://www.mdpi.com/2079-4983/6/2/259 |
| work_keys_str_mv | AT markrpickard usingmagneticnanoparticlesforgenetransfertoneuralstemcellsstemcellpropagationmethodinfluencesoutcomes AT christopherfadams usingmagneticnanoparticlesforgenetransfertoneuralstemcellsstemcellpropagationmethodinfluencesoutcomes AT perrinebarraud usingmagneticnanoparticlesforgenetransfertoneuralstemcellsstemcellpropagationmethodinfluencesoutcomes AT divyamchari usingmagneticnanoparticlesforgenetransfertoneuralstemcellsstemcellpropagationmethodinfluencesoutcomes |