Small extracellular vesicles promote cell survival and neuritogenesis in vitro in a manner dependent on dosage and cell of origin

Mesenchymal Stem Cells (MSC) possess a diverse secretome with well-established neuroprotective effects. Form among the materiel released by these cells, extracellular vesicles (EVs) have gained particular interest lately, owing to their good safety profile, stability, and relative ease of use as a cell-free therapy. These lipid-enclosed nano-carriers can significantly alter the survival of recipient cells through the delivery of a wide variety of signalling molecules, the exact composition of which is highly dependent on the type, age, and environment of the donor cells. Glaucoma is a chronic progressive optic neuropathy characterised by the loss of Retinal Ganglion Cells whose axons make up the optic nerve. Preservation of these neurons via the administration of the right EVs represents a promising approach for slowing disease progression, thereby preventing vision loss. Here, we evaluate and compare the protective and neuritogenic potential of small extracellular vesicles (sEVs), a subset of EVs with a diameter smaller than 220 nm, from six different cell types using a rodent in vitro model of RGC degeneration. Our findings showed that Adipose Mesenchymal Stem Cells release the most potent sEVs, with Bone Marrow being a close second. EVs released by cells of the Umbilical Cord, Dental Pulp, Dermal Fibroblasts, and an Oral Mucosal Lamina Propria-Progenitor cells did not have an observable benefit. Thus, our study provides greater insight into how the efficacy of different EVs compares to each other.