Comparative Analysis of In Vitro Neuroprotection and Neuritogenesis on Axotomised Retinal Ganglion Cells by Small Extracellular Vesicles Derived from Various Mesenchymal Stem Cells

The paracrine neuroprotective effects of Mesenchymal Stem Cells (MSC) are well known, and our understanding of the underlying mechanisms is expanding by the day. From among their diverse secretome, 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. The cargo and thus the potential effect of these nano-sized lipid membrane-enclosed vesicles is highly dependent on the type, age, and environment of the donor cells. Therefore, it is paramount to know which cell types are best utilised in any given situation. Glaucoma is a chronic progressive optic neuropathy that is the most common cause of irreversible blindness worldwide, characterised by the loss of Retinal Ganglion Cells (RGC) whose axons make up the optic nerve. Preservation of these neurons via the administration of the right EVs represents a promising approach for slowing down or halting disease progression, thereby preventing vision loss. Here, we evaluate the neuroprotective and neuritogenic potential of EVs isolated from five different cell types using a rodent in vitro model of RGC degeneration. Our findings showed that Adipose Mesenchymal Stem Cells (ADSC) release the most potent EVs, with Bone Marrow (BMSC) being a close second. EVs released by cells of the Umbilical Cord (UCSC), Dental Pulp (DPSC), Dermal Fibroblasts (DF), and an Oral Mucosal Lamina Propria-Progenitor cells (OMLP-PCs) did not have an observable benefit. Thus, our study provides greater insight into how the efficacy of different EVs compare to each other.