Antonietta Gentile

Publications (7)18.59 Total impact

• Source

  Available from: Gabriele Toietta

  Article: ANALYSIS OF BIODISTRIBUTION AND ENGRAFTMENT INTO THE LIVER OF GENETICALLY-MODIFIED MESENCHYMAL STROMAL CELLS DERIVED FROM ADIPOSE TISSUE.

  Giuliana Di Rocco, Antonietta Gentile, Annalisa Antonini, Silvia Truffa, Giulia Piaggio, Maurizio C Capogrossi, Gabriele Toietta
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  ABSTRACT: Presently, orthotopic liver transplant is the major therapeutic option for patients affected by primary liver diseases. This procedure is characterized by major invasive surgery, scarcity of donor organs, high costs, and lifelong immunosuppressive treatment. Transplant of hepatic precursor cells represents an attractive alternative. These cells could be used either for allogeneic transplantation or for autologous transplant after ex vivo genetic modification. We used stromal cells isolated from adipose tissue (AT-SCs) as platforms for autologous cell-mediated gene therapy. AT-SCs were transduced with lentiviral vectors expressing firefly luciferase, allowing for transplanted cell tracking by bioluminescent imaging (BLI). As a complementary approach, we followed circulating human α1-antitrypsin (hAAT) levels after infusion of AT-SCs overexpressing hAAT. Cells were transplanted into syngeneic mice after CCl₄-induced hepatic injury. Luciferase bioluminescence signals and serum hAAT levels were measured at different time points after transplantation and demonstrate persistence of transplanted cells for up to 2 months after administration. These data, along with immunohistochemical analysis, suggest engraftment and repopulation of injured livers by transplanted AT-SCs. Moreover, by transcriptional targeting using cellular tissue-specific regulatory sequences we confirmed that AT-SCs differentiate towards a hepatogenic-like phenotype in vitro and in vivo. Additionally, in transplanted cells re-isolated from recipient animals ' livers we detected activation of the alpha-fetoprotein (AFP) promoter. This promoter is normally transcriptionally silenced in adult tissues but can be re-activated during liver regeneration, suggesting commitment towards hepatogenic-like differentiation of engrafted cells in vivo. Our data support AT-SC cell-mediated gene therapy as an innovative therapeutic option for disorders of liver metabolism.
  Cell Transplantation 03/2012; · 5.13 Impact Factor
• Article: Gastric inhibitory polypeptide and its receptor are expressed in the central nervous system and support neuronal survival.

  Sabrina Paratore, Maria Teresa Ciotti, Magali Basille, David Vaudry, Antonietta Gentile, Rosalba Parenti, Pietro Calissano, Sebastiano Cavallaro
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  ABSTRACT: The development of neuronal apoptosis depends on an intrinsic transcriptional program. By DNA microarray technology, we have previously implicated a number of genes in different paradigms of neuronal apoptosis. In the present study, we investigated the spatiotemporal pattern of expression of two of these genes, gastric inhibitory polypeptide (Gip) and its receptor (Gipr) in the rat central nervous system. The levels of their transcripts were measured with real-time quantitative polymerase chain reaction and in situ-hybridization. Widespread expression of Gip and Gipr was found in adult rat brain, whereas during postnatal cerebellum development, they were highly expressed in the external and internal granule layer, and in Purkinje cells. To investigate the possible biological function of Gip we examined its effects in vitro. Addition of Gip to cultured cerebellar granule neurons reduced the extent of apoptotic death induced by switching the growing medium from 25 to 5 mM K+. This neurotrophic effect was mimicked by that of PACAP38 and IGF1. We conclude that Gip acts as an endogenous neurotrophic factor and supports neuronal survival.
  Central Nervous System Agents in Medicinal Chemistry(Formerly Current Medicinal Chemistry - Central Nervous System Agents) 09/2011; 11(3):210-22.
• Source

  Available from: Rosalba Parenti

  Article: Gastric Inhibitory Polypeptide and its Receptor are Expressed in the Central Nervous System and Support Neuronal Survival

  Sabrina Paratore, Maria Teresa Ciotti, Magali Basille, David Vaudry, Antonietta Gentile, Rosalba Parenti, Pietro Calissano, Sebastiano Cavallaro
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  ABSTRACT: The development of neuronal apoptosis depends on an intrinsic transcriptional program. By DNA microarray technology, we have previously implicated a number of genes in different paradigms of neuronal apoptosis. In the present study, we investigated the spatiotemporal pattern of expression of two of these genes, gastric inhibitory polypeptide (Gip) and its receptor (Gipr) in the rat central nervous system. The levels of their transcripts were measured with real-time quantitative polymerase chain reaction and in situ-hybridization. Widespread expression of Gip and Gipr was found in adult rat brain, whereas during postnatal cerebellum development, they were highly expressed in the external and internal granule layer, and in Purkinje cells. To investigate the possible biological function of Gip we examined its effects in vitro. Addition of Gip to cultured cerebellar granule neurons reduced the extent of apoptotic death induced by switching the growing medium from 25 to 5 mM K+. This neurotrophic effect was mimicked by that of PACAP38 and IGF1. We conclude that Gip acts as an endogenous neurotrophic factor and supports neuronal survival.
  Central Nervous System Agents in Medicinal Chemistry(Formerly Current Medicinal Chemistry - Central Nervous System Agents) 08/2011; 11(3):210-222.
• Source

  Available from: Gabriele Toietta

  Article: Human epicardium-derived cells fuse with high efficiency with skeletal myotubes and differentiate toward the skeletal muscle phenotype: a comparison study with stromal and endothelial cells.

  Antonietta Gentile, Gabriele Toietta, Vincenzo Pazzano, Vasileios D Tsiopoulos, Ada Francesca Giglio, Filippo Crea, Giulio Pompilio, Maurizio C Capogrossi, Giuliana Di Rocco
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  ABSTRACT: Recent studies have underscored a role for the epicardium as a source of multipotent cells. Here, we investigate the myogenic potential of adult human epicardium-derived cells (EPDCs) and analyze their ability to undergo skeletal myogenesis when cultured with differentiating primary myoblasts. Results are compared to those obtained with mesenchymal stromal cells (MSCs) and with endothelial cells, another mesodermal derivative. We demonstrate that EPDCs spontaneously fuse with pre-existing myotubes with an efficiency that is significantly higher than that of other cells. Although at a low frequency, endothelial cells may also contribute to myotube formation. In all cases analyzed, after entering the myotube, nonmuscle nuclei are reprogrammed to express muscle-specific genes. The fusion competence of nonmyogenic cells in vitro parallels their ability to reconstitute dystrophin expression in mdx mice. We additionally show that vascular cell adhesion molecule 1 (VCAM1) expression levels of nonmuscle cells are modulated by soluble factors secreted by skeletal myoblasts and that VCAM1 function is required for fusion to occur. Finally, treatment with interleukin (IL)-4 or IL-13, two cytokines released by differentiating myotubes, increases VCAM1 expression and enhances the rate of fusion of EPDCs and MSCs, but not that of endothelial cells.
  Molecular biology of the cell 01/2011; 22(5):581-92. · 5.98 Impact Factor
• Source

  Available from: Gabriele Toietta

  Article: Enhanced healing of diabetic wounds by topical administration of adipose tissue-derived stromal cells overexpressing stromal-derived factor-1: biodistribution and engraftment analysis by bioluminescent imaging.

  Giuliana Di Rocco, Antonietta Gentile, Annalisa Antonini, Francesca Ceradini, Joseph C Wu, Maurizio C Capogrossi, Gabriele Toietta
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  ABSTRACT: Chronic ulcers represent a major health problem in diabetic patients resulting in pain and discomfort. Conventional therapy does not guarantee adequate wound repair. In diabetes, impaired healing is partly due to poor endothelial progenitor cells mobilisation and homing, with altered levels of the chemokine stromal-derived factor-1 (SDF-1) at the wound site. Adipose tissue-associated stromal cells (AT-SCs) can provide an accessible source of progenitor cells secreting proangiogenic factors and differentiating into endothelial-like cells. We demonstrated that topical administration of AT-SCs genetically modified ex vivo to overexpress SDF-1, promotes wound healing into diabetic mice. In particular, by in vivo bioluminescent imaging analysis, we monitored biodistribution and survival after transplantation of luciferase-expressing cells. In conclusion, this study indicates the therapeutic potential of AT-SCs administration in wound healing, through cell differentiation, enhanced cellular recruitment at the wound site, and paracrine effects associated with local growth-factors production.
  Stem cells international. 01/2010; 2011:304562.
• Article: Spontaneous aggregation and altered intracellular distribution of endogenous alpha-synuclein during neuronal apoptosis.

  Antonietta Gentile, Giuseppina Amadoro, Veronica Corsetti, Maria T Ciotti, Annalucia Serafino, Pietro Calissano
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  ABSTRACT: The precursor of the non-amyloid-beta component of Alzheimer's disease amyloid (NACP), also known as alpha-synuclein, is a presynaptic terminal molecule that accumulates in the senile plaques of Alzheimer's disease. Aberrant accumulation of this protein into insoluble aggregates has also been implicated in the pathogenesis of many other neurodegenerative diseases, collectively referred to as synucleinopathies. However, the precise pathogenetic mechanism that leads to aggregate formation and the consequent cellular damage remains elusive. Analyzing differentiated primary cultures of cerebellar granule neurons undergoing apoptosis due to K+ reduction from 25 mM to 5.0 mM, a neuronal model widely used to study event linking apoptosis and neurodegeneration [1], we assessed that endogenous monomeric alpha-synuclein decreases and spontaneously aggregates into detergent-insoluble high molecular species. Apoptosis is also correlated with a marked redistribution/accumulation of this protein from terminal neurites to perikaria, with formation of compact inclusion bodies in juxta-nuclear area. In addition, secretion of monomeric alpha-synuclein decreases in response to apoptotic stimulus, while part of it aggregates into fibrillar structures and becomes detectable by immunogold-electron microscope analysis. The data presented in this study demonstrate that an apoptotic event caused by a "physiological" trigger, such as neuronal membrane repolarization of cultured cerebellar granule neurons, induces alpha-synuclein intracellular redistribution and aggregation, two molecular events reminiscent of those occurring in different human neurodegenerative diseases all characterized by alpha-synuclein-positive inclusions. Our study indicates this in vitro neuronal system as an excellent model to dissect pathogenic mechanism(s).
  Journal of Alzheimer's disease: JAD 04/2008; 13(2):151-60. · 3.74 Impact Factor
• Article: Apoptotic death induces Abeta production and fibril formation to a much larger extent than necrotic-like death in CGNs.

  Simona Cicconi, Antonietta Gentile, Maria Teresa Ciotti, Tiziana Parasassi, Annalucia Serafino, Pietro Calissano
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  ABSTRACT: In this study we report that apoptotic death of primary cultures of cerebellar granule neurons is accompanied by release of thioflavin-binding proteins - indicative of the presence of beta-sheet structures - and fibril formation in the culture medium. When the same neurons are subjected to an excytotoxic death caused by 100 microM glutamate exposure, the amount of thioflavin binding is markedly reduced. Western blot analysis shows that fibrils contain monomers, dimers and trimers of amyloid-beta (Abeta) which, when observed at the electron microscope, have morphologies reminiscent of fibrils of senile plaques. These findings demonstrate that triggering an apoptotic pathway leads to beta-sheet transition and fibril formation of a protein primarily involved in Alzheimer's disease and may be of direct relevance to the possible link between apoptosis and this neuropathology.
  Journal of Alzheimer's disease: JAD 12/2007; 12(3):211-20. · 3.74 Impact Factor