title: REAC technology and hyaluron synthase 2, an interesting network to slow down stem cell senescence.
abstract: Hyaluronic acid (HA) plays a fundamental role in cell polarity and hydrodynamic processes, affording significant modulation of proliferation, migration, morphogenesis and senescence, with deep implication in the ability of stem cells to execute their differentiating plans. The Radio Electric Asymmetric Conveyer (REAC) technology is aimed to optimize the ions fluxes at the molecular level in order to optimize the molecular mechanisms driving cellular asymmetry and polarization. Here, we show that treatment with 4-methylumbelliferone (4-MU), a potent repressor of type 2 HA synthase and endogenous HA synthesis, dramatically antagonized the ability of REAC to recover the gene and protein expression of Bmi1, Oct4, Sox2, and Nanog in ADhMSCs that had been made senescent by prolonged culture up to the 30(th) passage. In senescent ADhMSCs, 4-MU also counteracted the REAC ability to rescue the gene expression of TERT, and the associated resumption of telomerase activity. Hence, the anti-senescence action of REAC is largely dependent upon the availability of endogenous HA synthesis. Endogenous HA and HA-binding proteins with REAC technology create an interesting network that acts on the modulation of cell polarity and intracellular environment. This suggests that REAC technology is effective on an intracellular niche level of stem cell regulation.
authors.affiliation: Center for developmental biology and reprogramming - CEDEBIOR, Department of Biomedical Sciences, University of Sassari Viale San Pietro 43/B, 07100 Sassari, Italy.|Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Monserrato, Cagliari, Italy.|Department of Regenerative Medicine, Rinaldi Fontani Institute, Viale Belfiore 43, 50144 Florence, Italy.|National Institute of Biostructures and Biosystems at the Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola - Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Maioli
authors.affiliation: Department of Regenerative Medicine, Rinaldi Fontani Institute, Viale Belfiore 43, 50144 Florence, Italy.|Department of Anti Aging Medicine, Rinaldi Fontani Institute, Viale Belfiore 43, 50144 Florence, Italy.|Research Department, Rinaldi Fontani Foundation, Viale Belfiore 43, 50144 Florence, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Rinaldi
authors.affiliation: Center for developmental biology and reprogramming - CEDEBIOR, Department of Biomedical Sciences, University of Sassari Viale San Pietro 43/B, 07100 Sassari, Italy.|National Institute of Biostructures and Biosystems at the Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola - Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Pigliaru
authors.affiliation: Center for developmental biology and reprogramming - CEDEBIOR, Department of Biomedical Sciences, University of Sassari Viale San Pietro 43/B, 07100 Sassari, Italy.|National Institute of Biostructures and Biosystems at the Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola - Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Santaniello
authors.affiliation: Center for developmental biology and reprogramming - CEDEBIOR, Department of Biomedical Sciences, University of Sassari Viale San Pietro 43/B, 07100 Sassari, Italy.|Research Department, Rinaldi Fontani Foundation, Viale Belfiore 43, 50144 Florence, Italy.|Department of Biotechnology, University of Natural Resources and Life Sciences Vienna, Muthgasse 18, A-1190 Vienna, Austria.
authors.forename: Valentina
authors.initials: V
authors.lastname: Basoli
authors.affiliation: Department of Regenerative Medicine, Rinaldi Fontani Institute, Viale Belfiore 43, 50144 Florence, Italy.|Department of Anti Aging Medicine, Rinaldi Fontani Institute, Viale Belfiore 43, 50144 Florence, Italy.|Research Department, Rinaldi Fontani Foundation, Viale Belfiore 43, 50144 Florence, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Castagna
authors.affiliation: Department of Regenerative Medicine, Rinaldi Fontani Institute, Viale Belfiore 43, 50144 Florence, Italy.|Department of Anti Aging Medicine, Rinaldi Fontani Institute, Viale Belfiore 43, 50144 Florence, Italy.
authors.forename: Vania
authors.initials: V
authors.lastname: Fontani
authors.affiliation: National Institute of Biostructures and Biosystems at the Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola - Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.|Stem Wave Institute for Tissue Healing (SWITH), Ettore Sansavini Health Science Foundation- NPO, via Provinciale per Cotignola 9, 48022 Lugo (Ravenna), Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Ventura
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D002454:Cell Differentiation; D016922:Cellular Senescence; D004558:Electric Stimulation; D004560:Electricity; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D000076002:Hyaluronan Synthases / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000737:chemistry; D006923:Hymecromone / Q000494:pharmacology; D000071317:Nanog Homeobox Protein / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism; D011846:Radio Waves; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology; D019098:Telomerase / Q000378:metabolism
chemical_list: C069077:BMI1 protein, human; D018960:Hyaluronan Receptors; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D006923:Hymecromone; D006820:Hyaluronic Acid; D019001:Nitric Oxide Synthase; D063150:Polycomb Repressive Complex 1; C101754:HAS2 protein, human; D000076002:Hyaluronan Synthases; D019098:Telomerase