1. Ex Vivo Molecular Rejuvenation Improves the Therapeutic Activity of Senescent Human Cardiac Stem Cells in a Mouse Model of Myocardial InfarctionElisa Avolio, Giuseppe Gianfranceschi, Angela Caragnano, Emmanouil Athanasakis, Rajesh Katare, Daniela Cesselli, Marco Meloni, Anita Palma, Arianna Barchiesi, Carlo Vascotto, Barbara Toffoletto, Elisa Mazzega, Nicoletta Finato, Giuseppe Aresu, Ugolino Livi, Costanza Emanueli, Giacinto Scoles, Carlo Alberto Beltrami, Paolo Madeddu, Antonio Paolo Beltrami, 2014, original scientific article Abstract: Cardiac stem cells (CSC) from explanted decompensated hearts (E-CSC) are, with respect to those obtained from healthy donors (D-CSC), senescent and functionally impaired. We aimed to identify alterations in signaling pathways that are associated with CSC senescence. Additionally, we inves- tigated if pharmacological modulation of altered pathways can reduce CSC senescence in vitro and enhance their reparative ability in vivo. Measurement of secreted factors showed that E-CSC release larger amounts of proinflammatory cytokine IL1b compared with D-CSC. Using blocking antibodies, we verified that IL1b hampers the paracrine protective action of E-CSC on cardiomyo- cyte viability. IL1b acts intracranially inducing IKKb signaling, a mechanism that via nuclear factor-jB upregulates the expression of IL1b itself. Moreover, E-CSC show reduced levels of AMP protein kinase (AMPK) activating phosphorylation. This latter event, together with enhanced IKKb signaling, increases TORC1 activity, thereby impairing the autophagic flux and inhibiting the phos- phorylation of Akt and cAMP response element-binding protein. The combined use of rapamycin and resveratrol enhanced AMPK, thereby restoring downstream signaling and reducing IL1b secretion. These molecular corrections reduced E-CSC senescence, re-establishing their protective activity on cardiomyocytes. Moreover ex vivo treatment with rapamycin and resveratrol improved E-CSC capacity to induce cardiac repair upon injection in the mouse infarcted heart, leading to reduced cardiomyocyte senescence and apoptosis and increased abundance of endog- enous c-Kit1 CSC in the peri-infarct area. Molecular rejuvenation of patient-derived CSC by short pharmacologic conditioning boosts their in vivo reparative abilities. This approach might prove useful for refinement of CSC-based therapies.
Keywords: Stem cells, Myocardial infarction, Cellular senescence, Heart failure
Published in RUNG: 21.03.2017; Views: 4834; Downloads: 0
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2. Hair cortisol as a marker of hypothalamic-pituitary-adrenal axis activation in Friesian dairy cows clinically or physiologically compromisedTanja Peric, A. Comin, M. Corazzin, A. Prandi, M. C. Veronesi, T. Meloni, V. Zufferli, G. Cornacchia, 2013, original scientific article Keywords: govedo, dlake, kortizol
Published in RUNG: 16.06.2016; Views: 4982; Downloads: 24
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3. Do enviromental factors influence hair cortisol in foaling season?Tanja Peric, A. Comin, M. Montillo, A. Prandi, T. Meloni, Massimo Faustini, F Cairoli, 2012, published scientific conference contribution abstract Keywords: dlaka, kortizol, žrebe
Published in RUNG: 16.06.2016; Views: 4683; Downloads: 25
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4. Individual hair cortisol as a tool for monitoring HPA activity in healthy dairy cowsTanja Peric, A. Comin, M. Montillo, A. Prandi, T. Meloni, V. Zufferli, Massimo Faustini, S Pantaleo, 2012, published scientific conference contribution Keywords: dlaka, kortizol, krave molznice
Published in RUNG: 16.06.2016; Views: 6251; Downloads: 22
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5. Insulin-like growth factor I plasma concentrations in newborn healthy donkey and horse foalsTanja Peric, A. Comin, M. Montillo, A. Prandi, T. Meloni, Augusto Carluccio, I. De Amicis, S. Panzani, 2013, published scientific conference contribution abstract Keywords: rastni hormon, plazemske koncentracije, žrebeta
Published in RUNG: 16.06.2016; Views: 5172; Downloads: 23
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6. Cortisol hair and nails concentrations in newborn puppies and kittens : preliminary resultsTanja Peric, M. Montillo, A. Prandi, M. C. Veronesi, T. Meloni, Alessandro Rota, 2012, published scientific conference contribution Keywords: psi, mačke, mladički, dlaka, kortizol, kremplji
Published in RUNG: 10.07.2015; Views: 6506; Downloads: 37
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7. IGF-I, NEFA and cortisol concentrations in fetal fluids of dogs and cats : preliminary dataTanja Peric, A. Comin, M. C. Veronesi, T. Meloni, Alessandro Rota, MC Pisu, 2012, published scientific conference contribution Keywords: psi, mačke, fetalne tekočine, hormoni, presnovni dejavniki
Published in RUNG: 10.07.2015; Views: 6440; Downloads: 43
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