Stem cell secretome- and extracellular vesicle-based therapies for retinal pathologies

Figure 1 Schematic representation of stem cell secretome- and extracellular vesicle-mediated retinal protection. Stem cells, including mesenchymal stem cells, progenitor cells, and induced pluripotent stem cells, release a secretome comprising non-vesicular soluble mediators and extracellular vesicles (EVs). The non-vesicular fraction includes soluble cytokines, chemokines, growth factors, and trophic factors, whereas EVs may carry proteins, enzymes, lipids, DNA, messenger RNA, microRNAs, and other non-coding RNAs. These components interact with photoreceptors, retinal ganglion cells, retinal pigment epithelial cells, Müller cells, microglia, and endothelial cells, modulating inflammation, oxidative stress, apoptosis, glial activation, vascular dysfunction, and neuronal degeneration. The resulting anti-inflammatory, antioxidant, anti-apoptotic, neurotrophic, and vascular-stabilizing effects may support retinal homeostasis, photoreceptor preservation, retinal ganglion cell survival, reduced tissue damage, and disease modification. The two fractions are represented schematically and are not mutually exclusive, because some cytokines, growth factors, receptors, and other proteins may also be associated with EVs. This figure is conceptual and hypothesis-generating. The pathways shown summarize predominantly preclinical evidence and should not be interpreted as indicating that all mechanisms are simultaneously operative, causally established, or clinically validated. In accordance with MISEV2023, EV is used as the generic term when vesicle biogenesis has not been established; the term “exosome” is reserved for preparations with evidence supporting endosomal origin or when reproducing source-study terminology[11]. MSC: Mesenchymal stem cell; iPSC: Induced pluripotent stem cell; RPE: Retinal pigment epithelium; RGC: Retinal ganglion cell. Image(s) provided by Servier Medical Art (https://smart.servier.com), licensed under CC BY 4.0 (https://creativecommons.org/Licenses/by/4.0/).