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Abstract #81372 Published in IGR 20-3

Multipotent stem cell-derived retinal ganglion cells in 3D culture as tools for neurotrophic factor gene delivery system development

Chen DW; Narsineni L; Foldvari M
Nanomedicine: Nanotechnology, Biology, and Medicine 2019; 21: 102045


Non-viral neurotrophic factor (NF) gene therapy is a new paradigm in glaucoma treatment with the potential for neuroprotection and regeneration of damaged retinal ganglion cells (RGCs). To improve nanoparticle gene delivery systems and generate a suitable RGC cell model to facilitate in vitro investigations, we have developed mouse multipotent retinal stem cell (MRSC)-derived RGCs (XFC-3 cells) that express key RGC characteristics as demonstrated through biomarker expression profiling and stimuli-inducible neurite extension evaluation. Dicationic gemini surfactant-, single-walled carbon nanotube-, and K2-lipopolyamine polymer-based gene delivery systems were formulated and evaluated in three-dimensional (3D) A7/XFC-3 and XFC-3/XFC-3 co-cultures to validate the model for transfection efficiency (TE) and brain-derived neurotrophic factor (BDNF) bioactivity measurements, which helped identify the K2-NPs as having high TE (63.1% ± 1.4%) and high cell viability (94.4% ± 0.4%). Overall, XFC-3 cells are suitable for the construction of 3D in vivo-like tissue models and enable the screening of RGC-aimed gene delivery systems for neuroprotective treatment of glaucoma.

School of Pharmacy and Waterloo Institute of Nanotechnology, University of Waterloo, 200 University Avenue West, Waterloo, ON, Canada.

Full article

Classification:

11.9 Gene therapy (Part of: 11 Medical treatment)
2.17 Stem cells (Part of: 2 Anatomical structures in glaucoma)
11.8 Neuroprotection (Part of: 11 Medical treatment)



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