Calcium oscillations in mesenchymal stem cells, a control on cell cycle progression to influence cell fate towards proliferation or differentiation?

Abstract Background Under regular culture conditions, mesenchymal stem cells (MSCs) exhibit cytosolic calcium concentration oscillations (Ca2+ oscillations), that change, especially in frequency, after the differentiation of the MSCs. Ca2+ oscillations are known to encode important information in fr...

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Main Authors: Leslie A. Vallet, Marina Sánchez-Petidier, Romain Fernandes, Nataliia Naumova, Caterina Merla, Claudia Consales, Giorgia Innamorati, Franck M. André, Lluis M. Mir
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Stem Cell Research & Therapy
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Online Access:https://doi.org/10.1186/s13287-025-04454-8
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author Leslie A. Vallet
Marina Sánchez-Petidier
Romain Fernandes
Nataliia Naumova
Caterina Merla
Claudia Consales
Giorgia Innamorati
Franck M. André
Lluis M. Mir
author_facet Leslie A. Vallet
Marina Sánchez-Petidier
Romain Fernandes
Nataliia Naumova
Caterina Merla
Claudia Consales
Giorgia Innamorati
Franck M. André
Lluis M. Mir
author_sort Leslie A. Vallet
collection DOAJ
description Abstract Background Under regular culture conditions, mesenchymal stem cells (MSCs) exhibit cytosolic calcium concentration oscillations (Ca2+ oscillations), that change, especially in frequency, after the differentiation of the MSCs. Ca2+ oscillations are known to encode important information in frequency and amplitude, ultimately controlling many cellular processes such as proliferation and differentiation. Previous studies evidenced that decreasing the frequency of Ca2 + oscillations by physical means can facilitate osteodifferentiation of MSCs. Understanding the relationships between Ca2 + oscillations and MSCs proliferation or differentiation appears necessary in the attractive perspective of influencing cell fate by controlling Ca2 + signaling. Methods Using fluorescence microscopy we evaluated the evolution of Ca2+ oscillations throughout the adipogenic and osteogenic differentiation processes. Then, using electrical stimulation with microsecond pulsed electric fields (µsPEFs), we manipulated the frequency of Ca2+ oscillations in MSCs and measured its consequences on cell growth. Results Although the evolution of the Ca2 + oscillation frequencies differed between the adipogenic and osteogenic differentiation pathways in early stages of differentiation, we observed common features in the late stages: a progressive decrease in the Ca2 + oscillations frequencies, before their complete arrest as the differentiations reached their term. It has been reported that most cells undergoing differentiation experience a concomitant commitment to terminal differentiation and cell cycle exit, and prior to this, lengthened G1 phases, where the molecular competition between mitogenic and differentiating signals occurs. A relationship between the frequency of Ca2+ oscillations and the progression of the cell cycle, through some Ca2 + sensitive molecular factors, could explain the evolutions of the frequencies of Ca2+ oscillations observed during proliferation and differentiation. We hypothesized that increasing the frequency of Ca2+ oscillations would promote proliferation, while decreasing it would promote differentiation under differentiating conditions. Using electrical stimulation with µsPEFs, we manipulated the frequency of Ca2+ oscillations in MSCs and its increase actually promoted cell proliferation. Conclusions Manipulating the frequency of Ca2 + oscillations influences the cell fate of MSCs. We propose hypotheses on the actors that could link the Ca2 + oscillation frequencies with proliferation and differentiation processes, based on data available in the literature.
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spelling doaj-art-186dc7b3578a4e1b909df5812df127b42025-08-24T11:11:09ZengBMCStem Cell Research & Therapy1757-65122025-08-0116111410.1186/s13287-025-04454-8Calcium oscillations in mesenchymal stem cells, a control on cell cycle progression to influence cell fate towards proliferation or differentiation?Leslie A. Vallet0Marina Sánchez-Petidier1Romain Fernandes2Nataliia Naumova3Caterina Merla4Claudia Consales5Giorgia Innamorati6Franck M. André7Lluis M. Mir8Metabolic and Systemic Aspects of Oncogenesis for New Therapeutic Approaches (METSY), UMR 9018, CNRS, Gustave Roussy, Université Paris-SaclayMetabolic and Systemic Aspects of Oncogenesis for New Therapeutic Approaches (METSY), UMR 9018, CNRS, Gustave Roussy, Université Paris-SaclayMetabolic and Systemic Aspects of Oncogenesis for New Therapeutic Approaches (METSY), UMR 9018, CNRS, Gustave Roussy, Université Paris-SaclayMetabolic and Systemic Aspects of Oncogenesis for New Therapeutic Approaches (METSY), UMR 9018, CNRS, Gustave Roussy, Université Paris-SaclayDivision of Biotechnologies, Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA)Division of Biotechnologies, Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA)Division of Biotechnologies, Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA)Metabolic and Systemic Aspects of Oncogenesis for New Therapeutic Approaches (METSY), UMR 9018, CNRS, Gustave Roussy, Université Paris-SaclayMetabolic and Systemic Aspects of Oncogenesis for New Therapeutic Approaches (METSY), UMR 9018, CNRS, Gustave Roussy, Université Paris-SaclayAbstract Background Under regular culture conditions, mesenchymal stem cells (MSCs) exhibit cytosolic calcium concentration oscillations (Ca2+ oscillations), that change, especially in frequency, after the differentiation of the MSCs. Ca2+ oscillations are known to encode important information in frequency and amplitude, ultimately controlling many cellular processes such as proliferation and differentiation. Previous studies evidenced that decreasing the frequency of Ca2 + oscillations by physical means can facilitate osteodifferentiation of MSCs. Understanding the relationships between Ca2 + oscillations and MSCs proliferation or differentiation appears necessary in the attractive perspective of influencing cell fate by controlling Ca2 + signaling. Methods Using fluorescence microscopy we evaluated the evolution of Ca2+ oscillations throughout the adipogenic and osteogenic differentiation processes. Then, using electrical stimulation with microsecond pulsed electric fields (µsPEFs), we manipulated the frequency of Ca2+ oscillations in MSCs and measured its consequences on cell growth. Results Although the evolution of the Ca2 + oscillation frequencies differed between the adipogenic and osteogenic differentiation pathways in early stages of differentiation, we observed common features in the late stages: a progressive decrease in the Ca2 + oscillations frequencies, before their complete arrest as the differentiations reached their term. It has been reported that most cells undergoing differentiation experience a concomitant commitment to terminal differentiation and cell cycle exit, and prior to this, lengthened G1 phases, where the molecular competition between mitogenic and differentiating signals occurs. A relationship between the frequency of Ca2+ oscillations and the progression of the cell cycle, through some Ca2 + sensitive molecular factors, could explain the evolutions of the frequencies of Ca2+ oscillations observed during proliferation and differentiation. We hypothesized that increasing the frequency of Ca2+ oscillations would promote proliferation, while decreasing it would promote differentiation under differentiating conditions. Using electrical stimulation with µsPEFs, we manipulated the frequency of Ca2+ oscillations in MSCs and its increase actually promoted cell proliferation. Conclusions Manipulating the frequency of Ca2 + oscillations influences the cell fate of MSCs. We propose hypotheses on the actors that could link the Ca2 + oscillation frequencies with proliferation and differentiation processes, based on data available in the literature.https://doi.org/10.1186/s13287-025-04454-8Cell proliferationElectrical stimulationCell cycle controlMicrosecond pulsed electric fieldsElectroporationElectropermeabilization
spellingShingle Leslie A. Vallet
Marina Sánchez-Petidier
Romain Fernandes
Nataliia Naumova
Caterina Merla
Claudia Consales
Giorgia Innamorati
Franck M. André
Lluis M. Mir
Calcium oscillations in mesenchymal stem cells, a control on cell cycle progression to influence cell fate towards proliferation or differentiation?
Stem Cell Research & Therapy
Cell proliferation
Electrical stimulation
Cell cycle control
Microsecond pulsed electric fields
Electroporation
Electropermeabilization
title Calcium oscillations in mesenchymal stem cells, a control on cell cycle progression to influence cell fate towards proliferation or differentiation?
title_full Calcium oscillations in mesenchymal stem cells, a control on cell cycle progression to influence cell fate towards proliferation or differentiation?
title_fullStr Calcium oscillations in mesenchymal stem cells, a control on cell cycle progression to influence cell fate towards proliferation or differentiation?
title_full_unstemmed Calcium oscillations in mesenchymal stem cells, a control on cell cycle progression to influence cell fate towards proliferation or differentiation?
title_short Calcium oscillations in mesenchymal stem cells, a control on cell cycle progression to influence cell fate towards proliferation or differentiation?
title_sort calcium oscillations in mesenchymal stem cells a control on cell cycle progression to influence cell fate towards proliferation or differentiation
topic Cell proliferation
Electrical stimulation
Cell cycle control
Microsecond pulsed electric fields
Electroporation
Electropermeabilization
url https://doi.org/10.1186/s13287-025-04454-8
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