Murine adipose-derived mesenchymal stromal cell vesicles: in vitro clues for neuroprotective and neuroregenerative approaches.
OBJECTIVE
Adipose-derived mesenchymal stromal cells (ASC) are known to promote neuroprotection and neuroregeneration in vitro and in vivo. 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 in vitro.


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 in vitro 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.
Department of Neurological and Movement Sciences, University of Verona, Verona, Italy.
Alessia
A
Farinazzo
Department of Neurological and Movement Sciences, University of Verona, Verona, Italy.
Ermanna
E
Turano
Department of Neurological and Movement Sciences, University of Verona, Verona, Italy.
Silvia
S
Marconi
Department of Neurological and Movement Sciences, University of Verona, Verona, Italy.
Edoardo
E
Bistaffa
Department of Neurological and Movement Sciences, University of Verona, Verona, Italy.
Elena
E
Bazzoli
Department of Neurological and Movement Sciences, University of Verona, Verona, Italy. Electronic address: bruno.bonetti@univr.it.
Bruno
B
Bonetti
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D045744:Cell Line, Tumor; D055252:Cell-Derived Microparticles / Q000145:classification* / Q000378:metabolism / Q000648:ultrastructure; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008810:Mice, Inbred C57BL; D009416:Nerve Regeneration / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*
D018696:Neuroprotective Agents
mesenchymal stromal cells; microvesicles; nanovesicles; paracrine effect