Cholinergic effects mediated by M2 muscarinic receptor in human Schwann-like cells induced from adipose mesenchymal stem cells

Schwann cells (SCs) have an important role in peripheral nerve regeneration but there are several restrictions hindering their clinical application. Adipose derived stem cells (ASCs) feature good properties for cell therapies. When exposed to specific growth factors in vitro, they can acquire a SC-like phenotype (dASCs), expressing key SCs markers. Our group has demonstrated that M2 muscarinic receptor in rat dASCs causes a reversible arrest of cell proliferation, increasing SCs myelinating phenotype. Human dASCs, as rat dASCs, express muscarinic receptors. In the present work we evaluate if M2 muscarinic receptor activation may contribute to human dASCs proliferation, migration and phenotype. M2 selective activation by selective agonist Arecaidine Propargyl Ester (APE) causes a decreased cell proliferation, modulating the expression of genes involved in the proliferation/differentiation (i.e. c-jun and egr2) and several neurotrophic factors. Moreover, M2 selective activation is able to decrease cell migration. Although further analyses are needed to best characterise the role of M2 receptor, these results are the first evidence that its selective activation may have effects also on human dASCs proliferation and migration. This may improve our knowledge of these promising therapeutic cells for potential use in nerve regeneration.