Murine adipose-derived mesenchymal stromal cell vesicles: Invitro clues for neuroprotective and neuroregenerative approaches

Background aims: Adipose-derived mesenchymal stromal cells (ASC) are known to promote neuroprotection and neuroregeneration invitro and invivo. These biological effects are probably mediated by paracrine mechanisms. In recent years, nanovesicles (NV) and microvesicles (MV) have been shown to play a major role in cell-to-cell communication. We tested the efficacy of NV and MV obtained from ASC in mediating neuroprotection and neuroregeneration invitro. Methods: We exposed neuronal cells (both cell line and primary cultures) to oxidative stress in the presence or not of NV or MV. Results: In this experimental setting, we found that low doses of NV or MV protected neurons from apoptotic cell death. We then assessed the neuroregenerative effect of NV/MV in cerebellar slice cultures demyelinated with lysophosphatidylcholine. We observed that low but not higher doses of NV and MV increased the process of remyelination and activated nestin-positive oligodendroglial precursors. Conclusions: Taken together, our data invitro support the relevance of ASC vesicles as a source of protecting and regenerating factors that might modulate the microenvironment in neuro-inflammatory as well as in neurodegenerative disorders. The present findings may suggest that stromal cell-derived vesicles might represent a potential therapeutic tool, enabling the safe administration of stromal cell effector factors, avoiding the cellular counterpart.