title: Development of Multifunctional Magnetic Nanoparticles for Genetic Engineering and Tracking of Neural Stem Cells.
abstract: Genetic modification of cell transplant populations and cell tracking ability are key underpinnings for effective cell therapies. Current strategies to achieve these goals utilize methods which are unsuitable for clinical translation because of related safety issues, and multiple protocol steps adding to cost and complexity. Multifunctional magnetic nanoparticles (MNPs) offering dual mode gene delivery and imaging contrast capacity offer a valuable tool in this context. Despite their key benefits, there is a critical lack of neurocompatible and multifunctional particles described for use with transplant populations for neurological applications. Here, a systematic screen of MNPs (using a core shown to cause contrast in magnetic resonance imaging (MRI)) bearing various surface chemistries (polyethylenimine (PEI) and oxidized PEI and hybrids of oxidized PEI/alginic acid, PEI/chitosan and PEI/polyamidoamine) is performed to test their ability to genetically engineer neural stem cells (NSCs; a cell population of high clinical relevance for central nervous system disorders). It is demonstrated that gene delivery to NSCs can be safely achieved using two of the developed formulations (PEI and oxPEI/alginic acid) when used in conjunction with oscillating magnetofection technology. After transfection, intracellular particles can be detected by histological procedures with labeled cells displaying contrast in MRI (for real time cell tracking).
authors: Institute for Science and Technology in Medicine, Keele University, Staffordshire, ST55BG, United Kingdom.
authors: Christopher
authors: C
authors: Adams
authors: Department of Chemistry, Building 211 (the Gradel Centre), Room 303 (3rd floor), Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan, 5290002, Israel.
authors: Liron Limor
authors: LL
authors: Israel
authors: Department of Chemistry, Building 211 (the Gradel Centre), Room 303 (3rd floor), Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan, 5290002, Israel.
authors: Stella
authors: S
authors: Ostrovsky
authors: Centre for Pre-Clinical Imaging, Institute for Translational Medicine, Crown Street, University of Liverpool, Liverpool, L69 3BX, United Kingdom.
authors: Arthur
authors: A
authors: Taylor
authors: Centre for Pre-Clinical Imaging, Institute for Translational Medicine, Crown Street, University of Liverpool, Liverpool, L69 3BX, United Kingdom.
authors: Harish
authors: H
authors: Poptani
authors: Department of Chemistry, Building 211 (the Gradel Centre), Room 303 (3rd floor), Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan, 5290002, Israel.
authors: Jean-Paul
authors: JP
authors: Lellouche
authors: Institute for Science and Technology in Medicine, Keele University, Staffordshire, ST55BG, United Kingdom.
authors: Divya
authors: D
authors: Chari
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D058948:Cell Tracking / Q000379:methods*; D004247:DNA / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology*; D010316:Particle Size; D011094:Polyethyleneimine / Q000737:chemistry; D012038:Regeneration; D055672:Static Electricity; D014162:Transfection
chemical_list: D015415:Biomarkers; D058185:Magnetite Nanoparticles; D011094:Polyethyleneimine; D004247:DNA
keywords: cell tracking; cell transplantation; magnetic nanoparticle; magnetic resonance imaging; magnetofection