Cholinergic receptors contribute to maintain the quiescent status of adipose mesenchymal stem cells

Mesenchymal stem cells (MSCs), also known as stromal mesenchymal stem cells, are multipotent cells, which can be found in many tissues and organs as bone marrow and adipose tissue. In particular MSCs derived from Adipose tissue (ASCs) are an attractive cell source for regenerative medicine. Acetylcholine (ACh), the most important neurotransmitter in Central (CNS) and peripheral nervous system (PNS), plays a key roles also in non-neural tissue. Although MSCs express cholinergic receptors, their role has been poorly investigated. Analysis by RT-PCR have demonstrated that ASCs express several muscarinic and nicotinic receptor subtypes. In particular M2 mAChR and alpha7 nAChR expression was also confirmed by western blot analysis. In present work cholinergic effects were studied on rat ASCs. By MTT and FACS analysis we have demonstrated that M2 receptor activation caused a reversible reduction of cell proliferation. Moreover, by wound healing and transwell assays, we have also demonstrated that M2 receptors caused an inhibition of cell migration, indicating the ACh as possible modulator of ASCs proliferation and migration. Similarly to that observed for M2 receptor, preliminary data on α-7 nAChR demonstrate that this receptor is able to modulate cell proliferation and migration. Interestingly the activation of α-7 nAChR appears also up-regulate the expression of M2 receptor, suggesting a feedback positive loop between the muscarinic and nicotinic receptors. Our results indicate that ACh via M2 mAChR and α-7 nAChR, may contribute to the maintaining of the ASCs quiescent status. These data are the first evidence that ACh, might contribute to control ASCs physiology.