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Isolation of human amniotic stem cells from term placenta and their in vitro differentation in airway epithelium to correct CF phenotype

Carbone, Annalucia (2012) Isolation of human amniotic stem cells from term placenta and their in vitro differentation in airway epithelium to correct CF phenotype. [Doctoral Thesis]

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Abstract

Cystic fibrosis (CF) is a lethal autosomal recessive disorder due to mutations in the CF transmembrane conductance regulator (CFTR) gene, a cAMP-dependent chloride channel expressed on the apical side of epithelial cells. Although CF involves many organs with secretory/absorptive properties, including the liver, the main cause of morbidity and mortality is a chronic inflammatory lung disease. Because of its monogenic nature, and since the lung is easily accessible, CF has been a target disease for gene-based therapeutic intervention; however, this approach has given unsatisfied results in terms of efficiency of gene delivery to the lung and of efficacy outcomes. This partial success was due to the inefficiency of passing the mucus barrier overlying the epithelial cells and to the immune response against the gene therapy vectors. Cell therapy could be a more effective treatment because allogenic normal cells and autologous engineered cells express CFTR gene. Bone marrow-derived stem cells have been the first source evaluated for homing to the lung and curative potential, but the in vivo efficiency of bone marrow stem cells to differentiate in airways epithelium is very low (0.01–0.025%), as also demonstrated by different studies in CF mice. Recently, new cell sources for CF treatment have been characterized; MSCs from cord blood and amniotic fluid stem cells can differentiate in vitro and in vivo in airway epithelium. Stemming from these results on MSCs, and based on the demonstrated high plasticity of amniotic derived stem cells, after an extensive characterization of the expression of phenotypic and pluripotency markers by hAMSCs and their differentiative potential, we preliminarily evaluated their usefulness in CF by in vitro experiments using cocultures of hAMSCs and CF-respiratory epithelial cells.

Item Type:Doctoral Thesis
Date:08 March 2012
Tutor:Colombo, Carla, Conese, Massimo
PhD classes:Ciclo 24 > Terapia pediatrica e farmacologia dello sviluppo
Coordinator:Galanello, Renzo
Institution:Universita' degli Studi di Cagliari
Divisions:Dipartimenti (fino a dicembre 2011) > Dipartimento di Scienze biomediche e biotecnologie
Subjects:Area 05 - Scienze biologiche > BIO/13 Biologia applicata
Uncontrolled Keywords:Cystic fibrosis, human amniotic mesenchymal stem cells, placenta, fibrosi cistica, cellule staminali mesenchimali amniotiche
ID Code:677
Deposited On:14 Mar 2012 13:49

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