Ricerc@Sapienza

Peripheral nerve regeneration has an intrinsic ability to regenerate and it depends on glial SCs to create a favorable environment that enhances nerve regeneration. Schwann cells (SCs) are key regulators of peripheral nerve regeneration and axonal myelination. Although SCs are an attractive therapeutic option for peripheral nerve injuries, there are several restrictions on their clinical application. Adipose derived stem cells (ASCs) represent an attractive source for cell therapies. When exposed to selective growth factors, they can acquire a SC-like phenotype (dASCs) expressing key SC markers and adopting a spindle-shape morphology. Neurotransmitters receptors such as GABA and Acetylcholine (ACh) are expressed during nervous system development and they contribute to SCs differentiation and myelin formation. Our group has demonstrated that Acetylcholine, via M2 muscarinic receptors, causes a reversible arrest of cell proliferation in SCs, increasing myelin proteins expression. dASCs also express muscarinic receptors. In rat model, M2 receptor activation causes a reversible arrest of the cell growth, without affecting cell survival. Moreover, its activation inhibits dASCs migration. M2 receptor stimulation also causes a significant decrease in neurotrophins expression, accompanied by a decreased release of proNGF and mNGF forms. The apoptotic proNGF isoform (25kDa) is strongly reduced after M2 receptor stimulation. Our data suggest that M2 receptors may be relevant for dASCs maturation and myelination, perhaps in a similar way to that observed in SCs.
The main aim of the present project will be to evaluate if muscarinic receptors activation may contribute also to human SC and dASCs proliferation and/or differentiation. These results may have a relevant impact on therapeutic treatment of human peripheral nerve injury.