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      Membrane Potential Controls Adipogenic and Osteogenic Differentiation of Mesenchymal Stem Cells

      research-article
      Author(s): 1 , 2 , 1 , *
      Editor(s):
      Publication date (Electronic):
      Journal: PLoS ONE
      Publisher: Public Library of Science

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          Abstract

          Background

          Control of stem cell behavior is a crucial aspect of developmental biology and regenerative medicine. While the functional role of electrophysiology in stem cell biology is poorly understood, it has become clear that endogenous ion flows represent a powerful set of signals by means of which cell proliferation, differentiation, and migration can be controlled in regeneration and embryonic morphogenesis.

          Methodology/Principal Findings

          We examined the membrane potential (V mem) changes exhibited by human mesenchymal stem cells (hMSCs) undergoing adipogenic (AD) and osteogenic (OS) differentiation, and uncovered a characteristic hyperpolarization of differentiated cells versus undifferentiated cells. Reversal of the progressive polarization via pharmacological modulation of transmembrane potential revealed that depolarization of hMSCs prevents differentiation. In contrast, treatment with hyperpolarizing reagents upregulated osteogenic markers.

          Conclusions/Significance

          Taken together, these data suggest that the endogenous hyperpolarization is a functional determinant of hMSC differentiation and is a tractable control point for modulating stem cell function.

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          Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN.

          Min Zhao, Bing Song, Jin Pu … (2006)
          Wound healing is essential for maintaining the integrity of multicellular organisms. In every species studied, disruption of an epithelial layer instantaneously generates endogenous electric fields, which have been proposed to be important in wound healing. The identity of signalling pathways that guide both cell migration to electric cues and electric-field-induced wound healing have not been elucidated at a genetic level. Here we show that electric fields, of a strength equal to those detected endogenously, direct cell migration during wound healing as a prime directional cue. Manipulation of endogenous wound electric fields affects wound healing in vivo. Electric stimulation triggers activation of Src and inositol-phospholipid signalling, which polarizes in the direction of cell migration. Notably, genetic disruption of phosphatidylinositol-3-OH kinase-gamma (PI(3)Kgamma) decreases electric-field-induced signalling and abolishes directed movements of healing epithelium in response to electric signals. Deletion of the tumour suppressor phosphatase and tensin homolog (PTEN) enhances signalling and electrotactic responses. These data identify genes essential for electrical-signal-induced wound healing and show that PI(3)Kgamma and PTEN control electrotaxis.
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            PPAR-gamma: adipogenic regulator and thiazolidinedione receptor.

            B Spiegelman (1998)
            The past several years have seen an explosive increase in our understanding of the transcriptional basis of adipose cell differentiation. In particular, a key role has been illustrated for PPAR-gamma, a member of the nuclear hormone receptor superfamily. PPAR-gamma has also been recently identified as the major functional receptor for the thiazolidinedione class of insulin-sensitizing drugs. This review examines the evidence that has implicated this transcription factor in the processes of adipogenesis and systemic insulin action. In addition, several models are discussed that may explain how a single protein can be involved in these related but distinct physiological actions. I also point out several important areas where our knowledge is incomplete and more research is needed. Finally, I discuss how advances in our understanding of nuclear receptor function, particularly the docking of cofactors in a ligand-dependent fashion, should lead to improved drugs that utilize the PPAR-gamma system for the treatment of insulin resistance.
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              An overview of real-time quantitative PCR: applications to quantify cytokine gene expression.

              A Giulietti, L Overbergh, D Valckx … (2001)
              The analysis of cytokine profiles helps to clarify functional properties of immune cells, both for research and for clinical diagnosis. The real-time reverse transcription polymerase chain reaction (RT-PCR) is becoming widely used to quantify cytokines from cells, body fluids, tissues, or tissue biopsies. Being a very powerful and sensitive method it can be used to quantify mRNA expression levels of cytokines, which are often very low in the tissues under investigation. The method allows for the direct detection of PCR product during the exponential phase of the reaction, combining amplification and detection in one single step. In this review we discuss the principle of real-time RT-PCR, the different methodologies and chemistries available, the assets, and some of the pitfalls. With the TaqMan chemistry and the 7700 Sequence Detection System (Applied Biosystems), validation for a large panel of murine and human cytokines and other factors playing a role in the immune system is discussed in detail. In summary, the real-time RT-PCR technique is very accurate and sensitive, allows a high throughput, and can be performed on very small samples; therefore it is the method of choice for quantification of cytokine profiles in immune cells or inflamed tissues. Copyright 2001 Elsevier Science (USA).
              Article 0 comments Cited 238 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                : Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, USA )
                ISSN (Electronic): 1932-6203
                Publication date Collection: 2008
                Publication date (Electronic): 17 November 2008
                Volume: 3
                Issue: 11
                Electronic Location Identifier: e3737
                Affiliations
                [1 ]Department of Biomedical Engineering, Tufts University, Medford, Massachusetts, United States of America
                [2 ]Biology Department, and Tufts Center for Regenerative and Developmental Biology, Tufts University, Medford, Massachusetts, United States of America
                University of Michigan, United States of America
                Author notes

                Conceived and designed the experiments: SS ML DLK. Performed the experiments: SS. Analyzed the data: SS. Contributed reagents/materials/analysis tools: DLK. Wrote the paper: SS ML.

                Article
                Publisher ID: 08-PONE-RA-06076R1
                DOI: 10.1371/journal.pone.0003737
                PMC ID: 2581599
                PubMed ID: 19011685
                SO-VID: e01681aa-6fb9-46d4-9f6d-7f6db4ffe828
                Copyright © Sundelacruz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                Date received : 22 August 2008
                Date accepted : 28 October 2008
                Page count
                Pages: 15
                Categories
                Subject: Research Article
                Subject: Biotechnology/Bioengineering
                Subject: Cell Biology/Cell Signaling
                Subject: Cell Biology/Developmental Molecular Mechanisms

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                ScienceOpen disciplines: Uncategorized

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