TNFα-Mediated Priming of Mesenchymal Stem Cells Enhances Their Neuroprotective Effect on Retinal Ganglion Cells
| Autor: | Donald J. Zack, Stanislav I. Tomarev, Ben Mead, Xitiz Chamling, Zubair Ahmed |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Retinal Ganglion Cells Vascular Endothelial Growth Factor A Priming (immunology) exosomes Pharmacology Retinal ganglion Etanercept Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine PEDF medicine TNFα Animals Humans Nerve Growth Factors retinal ganglion cell Eye Proteins priming Cells Cultured Serpins Retina mesenchymal stem cells Tumor Necrosis Factor-alpha Mesenchymal stem cell Retinal General Medicine Neuroprotection 3. Good health 030104 developmental biology medicine.anatomical_structure Neuroprotective Agents glaucoma Retinal ganglion cell chemistry Cell culture 030220 oncology & carcinogenesis Female sense organs Visual Neuroscience extracellular vesicles Signal Transduction |
| Zdroj: | Investigative Ophthalmology & Visual Science Investigative Opthalmology & Visual Science |
| ISSN: | 1552-5783 0146-0404 |
| Popis: | Purpose To determine whether priming of bone marrow mesenchymal stem cells (MSCs) by signals from injured retina, particularly tumor necrosis factor α (TNFα), increase their exosomes’ neuroprotective efficacy on retinal ganglion cells (RGCs). Methods MSCs were primed with retinal cell culture conditioned medium, with or without the TNFα blocker etanercept or TNFα prior to isolation of exosomes. MSC conditioned medium or exosomes were added to rat retinal cultures or human stem cell–derived retinal ganglion cell (hRGC) cultures, and RGC neuroprotective effects were quantified. Luminex assays were used to compare primed versus unprimed exosomes. Results MSC conditioned medium and exosomes exerted a significant neuroprotective effect on injured rat and hRGC. This effect was significantly increased after MSCs were primed with retinal conditioned medium or TNFα. Blocking of TNFα signaling with etanercept prevented priming-induced RGC neuroprotective efficacy. Priming increased Pigment epithelium-derived factor (PEDF) and VEGF-AA exosomal abundance. Conclusions MSC exosomes promote RGC survival not just in rodent retinal cultures but also with hRGC. Their efficacy can be further enhanced through TNFα priming with the mechanism of action potentially mediated, at least in part, through increased levels of PEDF and VEGF-AA. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|