Dottorato in BIOLOGIA CELLULARE E DELLO SVILUPPO

Titolo della tesi: Expression and functional characterization of Acetylcholine M2 muscarinic receptor in rat and human Schwann-like adipose-derived stem cells

Schwann cells (SCs) play a central role in peripheral nervous system physiology and in the response to axon injury. However, there are several restrictions hindering their clinical application, such as the difficulty in collection and a slow in vitro expansion. Adipose-derived stem cells (ASCs) present good properties for peripheral nerve regeneration. When exposed to specific growth factors in vitro, they can acquire a SC-like phenotype (dASCs) expressing key SCs markers and assuming spindle-shaped morphology. Cholinergic receptors are potential pharmacological targets and in particular, M2 subtype, are present in SCs and are able to modulate several physiological processes. In the current work the role of M2 muscarinic receptor activation in controlling rat and human dASCs proliferation, neurotrophic factor production and differentiation was extensively evaluated. ASCs differentiation protocol is a chemical stimulation and after growth factors withdrawal, dASCs revert their morphology and gene expression towards ASCs phenotype. We show that M2 stimulation is able to maintain a spindle-like morphology and improved SCs phenotype. These data are the first evidence that human dASCs are cholinoceptive and respond in a similar way to muscarinic agonists as rat dASCs, improving dASCs terminal differentiation.