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| Item Type: | Article |
|---|---|
| Title: | Preclinical evaluation of a cell-based gene therapy using the Sleeping Beauty transposon system in choroidal neovascularization |
| Creators Name: | Hernandez, M., Recalde, S., Garcia-Garcia, L., Bezunartea, J., Miskey, C., Johnen, S., Diarra, S., Sebe, A., Rodriguez-Madoz, J.R., Pouillot, S., Marie, C., Izsvák, Z., Scherman, D., Kropp, M., Prosper, F., Thumann, G., Ivics, Z., Garcia-Layana, A. and Fernandez-Robredo, P. |
| Abstract: | Age-related macular degeneration (AMD) is a progressiveretinal disorder characterized by imbalanced pro- andantiangiogenic signals. The aim of this study was to evaluatethe effect ofex vivocell-based gene therapy with stable expres-sion of human pigment epithelium-derived factor (PEDF)release using the non-viralSleeping Beauty(SB100X) trans-poson system delivered by miniplasmids free of antibiotic resis-tance markers (pFAR4). Retinal pigment epithelial (RPE) cellsand iris pigment epithelial (IPE) cells were co-transfected withpFAR4-inverted terminal repeats (ITRs) CMV-PEDF-BGHand pFAR4-CMV-SB100X-SV40 plasmids. Laser-inducedchoroidal neovascularization (CNV) was performed in rats,and transfected primary cells (transfected RPE [tRPE] andtransfected IPE [tIPE] cells) were injected into the subretinalspace. The leakage and CNV areas, vascular endothelial growthfactor (VEGF), PEDF protein expression, metalloproteinases 2and 9 (MMP-2/9), and microglial/macrophage markers weremeasured. Injection with tRPE/IPE cells significantly reducedthe 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-2activity. Our data demonstrated thatex vivonon-viral genetherapy reduces CNV and could be an effective and safe thera-peutic option for angiogenic retinal diseases. |
| Keywords: | Angiogenesis, Iris Pigment Epithelial Cells (IPE), Retinal Pigment Epithelium (RPE), Pigment Epithelium Derived Factor (PEDF), Vascular Endothelial Growth Factor (VEGF), SB100X Transposase, Animals, Rats |
| Source: | Molecular Therapy - Methods and Clinical Development |
| ISSN: | 2329-0501 |
| Publisher: | Cell Press |
| Volume: | 15 |
| Page Range: | 403-417 |
| Date: | 13 December 2019 |
| Official Publication: | https://doi.org/10.1016/j.omtm.2019.10.013 |
| PubMed: | View item in PubMed |
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