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

Abstract 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 fo...

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Main Authors: Roberta Piovesana, Alessandro Faroni, Ada Maria Tata, Adam J. Reid
Format: Article
Language:English
Published: Nature Publishing Group 2025-04-01
Series:Cell Death Discovery
Online Access:https://doi.org/10.1038/s41420-025-02404-0
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author Roberta Piovesana
Alessandro Faroni
Ada Maria Tata
Adam J. Reid
author_facet Roberta Piovesana
Alessandro Faroni
Ada Maria Tata
Adam J. Reid
author_sort Roberta Piovesana
collection DOAJ
description Abstract 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.
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spelling doaj-art-e60be9f2ff054565a918c40e7fe469492025-08-20T03:10:09ZengNature Publishing GroupCell Death Discovery2058-77162025-04-0111111110.1038/s41420-025-02404-0Acetylcholine muscarinic M2 receptor maintains human Schwann-like adipose-derived phenotype in the absence of differentiating mediumRoberta Piovesana0Alessandro Faroni1Ada Maria Tata2Adam J. Reid3Department of Biology and Biotechnologies “Charles Darwin”, Sapienza, University of RomeBlond McIndoe Laboratories, Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science CentreDepartment of Biology and Biotechnologies “Charles Darwin”, Sapienza, University of RomeBlond McIndoe Laboratories, Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science CentreAbstract 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.https://doi.org/10.1038/s41420-025-02404-0
spellingShingle Roberta Piovesana
Alessandro Faroni
Ada Maria Tata
Adam J. Reid
Acetylcholine muscarinic M2 receptor maintains human Schwann-like adipose-derived phenotype in the absence of differentiating medium
Cell Death Discovery
title Acetylcholine muscarinic M2 receptor maintains human Schwann-like adipose-derived phenotype in the absence of differentiating medium
title_full Acetylcholine muscarinic M2 receptor maintains human Schwann-like adipose-derived phenotype in the absence of differentiating medium
title_fullStr Acetylcholine muscarinic M2 receptor maintains human Schwann-like adipose-derived phenotype in the absence of differentiating medium
title_full_unstemmed Acetylcholine muscarinic M2 receptor maintains human Schwann-like adipose-derived phenotype in the absence of differentiating medium
title_short Acetylcholine muscarinic M2 receptor maintains human Schwann-like adipose-derived phenotype in the absence of differentiating medium
title_sort acetylcholine muscarinic m2 receptor maintains human schwann like adipose derived phenotype in the absence of differentiating medium
url https://doi.org/10.1038/s41420-025-02404-0
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