Preclinical evaluation of a cell-based gene therapy using the sleeping beauty transposon system in choroidal neovascularization

Age-related macular degeneration (AMD) is a progressive retinal disorder characterized by imbalanced pro- and antiangiogenic signals. The aim of this study was to evaluate the effect of ex vivo cell-based gene therapy with stable expression of human pigment epithelium-derived factor (PEDF) release u...

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Autores: Hernandez, M. (María)|||/items/64ef42cb-3438-4cd6-b8db-8a01244368da, Recalde-Maestre, S. (Sergio)|||/items/1f021661-e027-480f-bd57-ce3bfb8e5a0e, Garcia-Garcia, L. (Laura)|||/items/c0a0bfa6-658c-4340-a6eb-3d19a987c4ab, Bezunartea, J. (Jaione)|||/items/8f33ef1e-c03e-4e9e-a141-06c02e0f39dd, Miskey, C. (Csaba)|||/items/bb0600c6-4bd4-45e1-9a64-6a2b65ab9b59, Johnen, S. (S.)|||/items/660a1cfe-6f14-4c61-bb62-400b34fc026b, Diarra, S. (Sabine)|||/items/88ad9b42-ac85-44da-88db-7b3d11507e6a, Sebe, A. (Attila)|||/items/738d7522-72ee-4aa5-a979-7d3158728dcd, Rodriguez-Madoz, J.R. (Juan Roberto)|||/items/9c21019b-aeba-4cdc-b78e-178a176da535, Pouillot, S. (Severine)|||/items/4f394d7e-2857-451e-8f63-f52c551347f4, Marie, C. (Corinne)|||/items/fe7bdeb6-7572-4703-9481-d3129c125051, Izsvák, Z. (Zsuzsanna)|||/items/899e418a-4bc7-4902-ba4b-81bd9d1e6a53, Scherman, D. (Daniel)|||/items/95940d29-9dd2-469c-85d8-0c96986aa6ba, Kropp, M. (Martina)|||/items/bca128e8-5d25-4a92-afed-6469549133c8, Prosper-Cardoso, F. (Felipe)|||/items/3d1b0b82-06c3-4e63-8280-e903dc4dc0c1, Thumann, G. (Gabriele)|||/items/22867fb2-2982-4875-98a0-523004b9ad98, Ivics, Z. (Zoltán)|||/items/41f3837a-936b-4644-a239-3684c8d275d4, Garcia-Layana, A. (Alfredo)|||/items/631fff44-be4e-42e5-ad3a-8f0f10305836, Fernandez-Robredo, P. (Patricia)|||/items/cebb4451-3415-44cf-811a-c5ae0b139604
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/63713
Acceso en línea:https://hdl.handle.net/10171/63713
Access Level:acceso abierto
Palabra clave:Angiogenesis
Iris pigment epithelial cells (IPE)
Retinal pigment epithelium (RPE)
Pigment epithelium derived factor (PEDF)
Vascular endothelial growth factor (VEGF)
SB100X transposase
Área de Terapia Celular
Descripción
Sumario:Age-related macular degeneration (AMD) is a progressive retinal disorder characterized by imbalanced pro- and antiangiogenic signals. The aim of this study was to evaluate the effect of ex vivo cell-based gene therapy with stable expression of human pigment epithelium-derived factor (PEDF) release using the non-viral Sleeping Beauty (SB100X) transposon system delivered by miniplasmids free of antibiotic resistance markers (pFAR4). Retinal pigment epithelial (RPE) cells and iris pigment epithelial (IPE) cells were co-transfected with pFAR4-inverted terminal repeats (ITRs) CMV-PEDF-BGH and pFAR4-CMV-SB100X-SV40 plasmids. Laser-induced choroidal neovascularization (CNV) was performed in rats, and transfected primary cells (transfected RPE [tRPE] and transfected IPE [tIPE] cells) were injected into the subretinal space. The leakage and CNV areas, vascular endothelial growth factor (VEGF), PEDF protein expression, metalloproteinases 2 and 9 (MMP-2/9), and microglial/macrophage markers were measured. Injection with tRPE/IPE cells significantly reduced the leakage area at 7 and 14 days and the CNV area at 7 days. There was a significant increase in PEDF and the PEDF/VEGF ratio with tRPE cells and a reduction in the MMP-2 activity. Our data demonstrated that ex vivo non-viral gene therapy reduces CNV and could be an effective and safe therapeutic option for angiogenic retinal diseases.

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