Acetylcholine muscarinic M2 receptor maintains human Schwann-like adipose-derived phenotype in the absence of differentiating medium

Human adipose-derived stem cells (ASCs), differentiated in vitro towards Schwann-like phenotype (hdASCs), have been suggested as an alternative source of Schwann cells (SCs). However, although they seem a good alternative, their differentiation is unstable, losing their SC-like phenotype following growth factor withdrawal. Rat and human SCs and rat dASCs have been characterized for acetylcholine M2 muscarinic receptor subtype that plays a strategic role in the regulation of their differentiation. Here, we evaluated the M2 muscarinic receptor activation in controlling hdASC proliferation and stabilization of the hdASC phenotype. In accordance with our data in rats, M2 stimulation results in a reversible decrease of cell growth and migration in hdASCs, negatively modulates proliferation markers and upregulates differentiation markers. Remarkably, hdASC differentiation can be stabilized by M2 receptor activation in the absence of differentiation media maintaining a spindle-shaped morphology and SC-like marker expression. These results show that the M2 receptor enhances the hdASC phenotype, maintaining the expression of key glial markers and supporting their pro-regenerative properties.