Effects of a combinatorial treatment with gene and cell therapy on retinal ganglion cell survival and axonal outgrowth after optic nerve injury
| Autor: | Marcelo F. Santiago, Luiza Rachel Pinheiro de Carvalho, William W. Hauswirth, Hilda Petrs-Silva, Leandro Coelho Teixeira-Pinheiro, Rosalia Mendez-Otero, Almir Jordão da Silva-Junior, Gabriel Nascimento-dos-Santos, Louise A. Mesentier-Louro |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
Retinal Ganglion Cells 0301 basic medicine Cell Survival Nerve Crush Central nervous system Cell- and Tissue-Based Therapy Biology Mesenchymal Stem Cell Transplantation Retina Cell therapy 03 medical and health sciences 0302 clinical medicine PEDF Cell Line Tumor Genetics medicine Animals Humans Nerve Growth Factors Rats Wistar Eye Proteins Molecular Biology Ganglion cell layer Serpins Mesenchymal stem cell Mesenchymal Stem Cells Optic Nerve Axons Neuroprotection Nerve Regeneration Gene Expression Regulation Neoplastic Disease Models Animal 030104 developmental biology medicine.anatomical_structure Retinal ganglion cell Optic Nerve Injuries 030220 oncology & carcinogenesis Optic nerve Cancer research Molecular Medicine Female |
| Zdroj: | Gene Therapy. 27:27-39 |
| ISSN: | 1476-5462 0969-7128 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink