Effects of a combinatorial treatment with gene and cell therapy on retinal ganglion cell survival and axonal outgrowth after optic nerve injury
After an injury, axons in the central nervous system do not regenerate over large distances and permanently lose their connections to the brain. Two promising approaches to correct this condition are cell and gene therapies. In the present work, we evaluated the neuroprotective and neuroregenerative...
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| Veröffentlicht in: | Gene therapy 2020-02, Vol.27 (1-2), p.27-39 |
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| creator | Nascimento-dos-Santos, Gabriel Teixeira-Pinheiro, Leandro Coelho da Silva-Júnior, Almir Jordão Carvalho, Luiza Rachel Pinheiro de Mesentier-Louro, Louise Alessandra Hauswirth, William W. Mendez-Otero, Rosalia Santiago, Marcelo Felippe Petrs-Silva, Hilda |
| description | After an injury, axons in the central nervous system do not regenerate over large distances and permanently lose their connections to the brain. Two promising approaches to correct this condition are cell and gene therapies. In the present work, we evaluated the neuroprotective and neuroregenerative potential of pigment epithelium-derived factor (PEDF) gene therapy alone and combined with human mesenchymal stem cell (hMSC) therapy after optic nerve injury by analysis of retinal ganglion cell survival and axonal outgrowth. Overexpression of PEDF by intravitreal delivery of AAV2 vector significantly increased Tuj1-positive cells survival and modulated FGF-2, IL-1ß, Iba-1, and GFAP immunostaining in the ganglion cell layer (GCL) at 4 weeks after optic nerve crush, although it could not promote axonal outgrowth. The combination of AAV2.PEDF and hMSC therapy showed a higher number of Tuj1-positive cells and a pronounced axonal outgrowth than unimodal therapy after optic nerve crush. In summary, our results highlight a synergistic effect of combined gene and cell therapy relevant for future therapeutic interventions regarding optic nerve injury. |
| doi_str_mv | 10.1038/s41434-019-0089-0 |
| format | Article |
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Two promising approaches to correct this condition are cell and gene therapies. In the present work, we evaluated the neuroprotective and neuroregenerative potential of pigment epithelium-derived factor (PEDF) gene therapy alone and combined with human mesenchymal stem cell (hMSC) therapy after optic nerve injury by analysis of retinal ganglion cell survival and axonal outgrowth. Overexpression of PEDF by intravitreal delivery of AAV2 vector significantly increased Tuj1-positive cells survival and modulated FGF-2, IL-1ß, Iba-1, and GFAP immunostaining in the ganglion cell layer (GCL) at 4 weeks after optic nerve crush, although it could not promote axonal outgrowth. The combination of AAV2.PEDF and hMSC therapy showed a higher number of Tuj1-positive cells and a pronounced axonal outgrowth than unimodal therapy after optic nerve crush. In summary, our results highlight a synergistic effect of combined gene and cell therapy relevant for future therapeutic interventions regarding optic nerve injury.</description><subject>13/100</subject><subject>13/21</subject><subject>13/51</subject><subject>14/1</subject><subject>14/19</subject><subject>14/34</subject><subject>14/63</subject><subject>42/44</subject><subject>631/378/1687</subject><subject>631/532/2074</subject><subject>631/532/489</subject><subject>631/61/201</subject><subject>Analysis</subject><subject>Animals</subject><subject>Axons</subject><subject>Axons - physiology</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell Biology</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival</subject><subject>Cell therapy</subject><subject>Cell- and Tissue-Based Therapy - methods</subject><subject>Central nervous system</subject><subject>Disease Models, Animal</subject><subject>Epithelium</subject><subject>Eye Proteins - 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Two promising approaches to correct this condition are cell and gene therapies. In the present work, we evaluated the neuroprotective and neuroregenerative potential of pigment epithelium-derived factor (PEDF) gene therapy alone and combined with human mesenchymal stem cell (hMSC) therapy after optic nerve injury by analysis of retinal ganglion cell survival and axonal outgrowth. Overexpression of PEDF by intravitreal delivery of AAV2 vector significantly increased Tuj1-positive cells survival and modulated FGF-2, IL-1ß, Iba-1, and GFAP immunostaining in the ganglion cell layer (GCL) at 4 weeks after optic nerve crush, although it could not promote axonal outgrowth. The combination of AAV2.PEDF and hMSC therapy showed a higher number of Tuj1-positive cells and a pronounced axonal outgrowth than unimodal therapy after optic nerve crush. In summary, our results highlight a synergistic effect of combined gene and cell therapy relevant for future therapeutic interventions regarding optic nerve injury.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31243393</pmid><doi>10.1038/s41434-019-0089-0</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0003-2428-9606</orcidid><orcidid>https://orcid.org/0000-0001-8961-2959</orcidid></addata></record> |
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| subjects | 13/100 13/21 13/51 14/1 14/19 14/34 14/63 42/44 631/378/1687 631/532/2074 631/532/489 631/61/201 Analysis Animals Axons Axons - physiology Biomedical and Life Sciences Biomedicine Cell Biology Cell Line, Tumor Cell Survival Cell therapy Cell- and Tissue-Based Therapy - methods Central nervous system Disease Models, Animal Epithelium Eye Proteins - metabolism Eye Proteins - pharmacology Female Fibroblast growth factor 2 Ganglion Gene Expression Gene Expression Regulation, Neoplastic - genetics Gene Therapy Genes Glial fibrillary acidic protein Health aspects Human Genetics Humans Male Mesenchymal Stem Cell Transplantation - methods Mesenchymal Stem Cells - metabolism Mesenchyme Nanotechnology Nerve Crush Nerve Growth Factors - metabolism Nerve Growth Factors - pharmacology Nerve Regeneration Neuroprotection Optic Nerve Optic Nerve Injuries - therapy Pigment epithelium-derived factor Rats, Wistar Retina Retinal Ganglion Cells - drug effects Retinal Ganglion Cells - metabolism Serpins - metabolism Serpins - pharmacology Stem cells Therapeutic applications Transplantation |
| title | Effects of a combinatorial treatment with gene and cell therapy on retinal ganglion cell survival and axonal outgrowth after optic nerve injury |
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