Therapeutic Potential of Stem Cells for Treating Retinal Ganglion Cell Degeneration in Optic Neuropathies
DOI:
https://doi.org/10.56294/mw2023149Keywords:
Stem Cells, Retinal Ganglion Cell (RGC), Human Periodontal Ligament-Derived Stem Cells (PDLSCS), Optic Neuropathies, Extracellular Vesicles (EVS)Abstract
Retinal ganglion cell (RGC) degeneration is a symbol of optic neuropathies, leading to progressive vision loss with limited therapeutic options. Stem cell-based medicines have gained recognition as a potential breakthrough strategy for neuro-protection and regeneration in such conditions. This research investigated the efficacy of Human Periodontal Ligament-Derived Stem Cells (PDLSCs) and the Extracellular Vesicles (EVs) of Optic Neuropathies in a rat model. PDLSCs were isolated, characterized, and transplanted either as whole cells or via their secreted EVs. The neuroprotective and regenerative effects were assessed at 15, 61, and 120 days post-injury through histological analysis, RGC survival counts, axonal regeneration assays, and functional restoration of visual pathways. Additionally, serum-deprived PDLSCs were used to evaluate their impact on neuroprotection compared to regular PDLSCs. PDLSC transplantation significantly enhanced RGC survival and reduced apoptosis for up to 120 days post-injury, with marked improvements observed at 15 and 61 days. Axonal regeneration along the optic nerve was evident, particularly at 120 days, demonstrating a sustained regenerative response. Similar neuroprotective effects were observed with serum-deprived PDLSCs, suggesting a potential role of paracrine signaling in their therapeutic action. However, transplantation of EVs isolated from PDLSCs failed to induce significant neuroprotection or axonal regeneration, indicating that direct cellular interaction can be essential for optimal therapeutic outcomes. These results support further exploration of PDLSCs as a viable cell therapy approach for neurodegenerative conditions affecting the optic nerve.
References
1. Cen LP, Ng TK. Stem cell therapy for retinal ganglion cell degeneration. Neural Regeneration Research. 2018 Aug 1;13(8):1352-3.https://doi.org/10.4103/1673-5374.235237
2. Boia R, Ruzafa N, Aires ID, Pereiro X, Ambrósio AF, Vecino E, Santiago AR. Neuroprotective strategies for retinal ganglion cell degeneration: current status and challenges ahead. International journal of molecular sciences. 2020 Mar 25;21(7):2262.https://doi.org/10.3390/ijms21072262
3. da Silva-Junior AJ, Mesentier-Louro LA, Nascimento-dos-Santos G, Teixeira-Pinheiro LC, Vasques JF, Chimeli-Ormonde L, Bodart-Santos V, de Carvalho LR, Santiago MF, Mendez-Otero R. Human mesenchymal stem cell therapy promotes retinal ganglion cell survival and target reconnection after optic nerve crush in adult rats. Stem Cell Research & Therapy. 2021 Dec;12:1-4.https://doi.org/10.1186/s13287-020-02130-7
4. VanderWall KB, Huang KC, Pan Y, Lavekar SS, Fligor CM, Allsop AR, Lentsch KA, Dang P, Zhang C, Tseng HC, Cummins TR. Retinal ganglion cells with a glaucoma OPTN (E50K) mutation exhibit neurodegenerative phenotypes when derived from three-dimensional retinal organoids. Stem Cell Reports. 2020 Jul 14;15(1):52-66.https://doi.org/10.1016/j.stemcr.2020.05.009
5. Behtaj S, Rybachuk M. Strategies on the application of stem cells based therapies for the treatment of optic neuropathies. Neural Regeneration Research. 2021 Jun 1;16(6):1190-1.https://orcid.org/0000-0001-6589-3119
6. Fu L, Kwok SS, Chan YK, Ming Lai JS, Pan W, Nie L, Shih KC. Therapeutic strategies for attenuation of retinal ganglion cell injury in optic neuropathies: concepts in translational research and therapeutic implications. BioMed research international. 2019;2019(1):8397521.
https://doi.org/10.1155/2019/8397521
7. Rabesandratana O, Goureau O, Orieux G. Pluripotent stem cell-based approaches to explore and treat optic neuropathies. Frontiers in neuroscience. 2018 Sep 20;12:651
https://doi.org/10.3389/fnins.2018.00651
9. Coco-Martin RM, Pastor-Idoate S, Pastor JC. Cell replacement therapy for retinal and optic nerve diseases: cell sources, clinical trials and challenges. Pharmaceutics. 2021 Jun 11;13(6):865.https://doi.org/10.3390/pharmaceutics13060865
10. Aneesh A, Liu A, Moss HE, Feinstein D, Ravindran S, Mathew B, Roth S. Emerging concepts in the treatment of optic neuritis: mesenchymal stem cell-derived extracellular vesicles. Stem Cell Research & Therapy. 2021 Dec;12:1-5.https://doi.org/10.1186/s13287-021-02645-7
11. Mesentier-Louro LA, Liao YJ. Optic nerve regeneration: considerations on treatment of acute optic neuropathy and end-stage disease. Current Ophthalmology Reports. 2019 Mar 15;7:11-20.https://doi.org/10.1007/s40135-019-00194-0.
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