Neural progenitor cell (NPC) transplantation possesses enormous potential for the treatment of disorders and injuries of the central nervous system, including the replacement of lost cells or the repair of host neural circuity after spinal cord injury (SCI). Importantly, cell-based therapies in this context still require improvements such as increased cell survival and host circuit integration, and we propose the implementation of optogenetics as a solution. Blue-light stimulation of NPCs engineered to ectopically express the excitatory light-sensitive protein channelrhodopsin-2 (ChR2-NPCs) prompted an influx of cations and a subsequent increase in proliferation and differentiation into oligodendrocytes and neurons and the polarization of astrocytes from a pro-inflammatory phenotype to a pro-regenerative/anti-inflammatory phenotype. Moreover, neurons derived from blue-light-stimulated ChR2-NPCs exhibited both increased branching and axon length and improved axon growth in the presence of axonal inhibitory drugs such as lysophosphatidic acid or chondroitin sulfate proteoglycan. Our results highlight the enormous potential of optogenetically stimulated NPCs as a means to increase neuroregeneration and improve cell therapy outcomes for enhancing better engraftments and cell identity upon transplantation in conditions such as SCI.

Mesenchymal stem cells (MSCs) have been shown to have therapeutic efficacy in different complex pathologies in feline species. This effect is attributed to the secretion of a wide variety of bioactive molecules and extracellular vesicles, such as exosomes, with significant paracrine activity, encompassed under the concept of the secretome. However, at present, the exosomes from feline MSCs have not yet been studied in detail. The objective of this study is to analyze and compare the protein profiles of the secretome as a whole and its exosomal fraction from feline adipose-derived MSCs (fAd-MSCs). For this, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Protein–Protein Interaction Networks Functional Enrichment Analysis (STRING) were utilized. A total of 239 proteins were identified in the secretome, and 228 proteins specific to exosomes were identified, with a total of 133 common proteins. The proteins identified in the secretome were located in the extracellular regions and in the cytoplasm, while the exosomal proteins were located mainly in the membrane, cytoplasm and cytosol. Regarding function, in the secretome, proteins involved in different metabolic pathways, in pathways related to the immune system and the endocrine system and in the processing of proteins in the endoplasmic reticulum predominated. In contrast, proteins specific to exosomes were predominantly associated with endocytosis, cell junctions, platelet activation and other cell signaling pathways. The possible future use of the secretome, or some of its components, such as exosomes, would provide a non-cell-based therapeutic strategy for the treatment of different diseases that would avoid the drawbacks of cell therapy.