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Amniotic Mesenchymal Stem Cells: A New Source for Hepatocyte-Like Cells and Induction of CFTR Expression by Coculture with Cystic Fibrosis Airway Epithelial Cells

Cystic fibrosis (CF) is a monogenic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, with lung and liver manifestations. Because of pitfalls of gene therapy, novel approaches for reconstitution of the airway epithelium and CFTR expression should be explored. In...

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Autores principales: Paracchini, Valentina, Carbone, Annalucia, Colombo, Federico, Castellani, Stefano, Mazzucchelli, Silvia, Di Gioia, Sante, Degiorgio, Dario, Seia, Manuela, Porretti, Laura, Colombo, Carla, Conese, Massimo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3270433/
https://www.ncbi.nlm.nih.gov/pubmed/22315512
http://dx.doi.org/10.1155/2012/575471
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author Paracchini, Valentina
Carbone, Annalucia
Colombo, Federico
Castellani, Stefano
Mazzucchelli, Silvia
Di Gioia, Sante
Degiorgio, Dario
Seia, Manuela
Porretti, Laura
Colombo, Carla
Conese, Massimo
author_facet Paracchini, Valentina
Carbone, Annalucia
Colombo, Federico
Castellani, Stefano
Mazzucchelli, Silvia
Di Gioia, Sante
Degiorgio, Dario
Seia, Manuela
Porretti, Laura
Colombo, Carla
Conese, Massimo
author_sort Paracchini, Valentina
collection PubMed
description Cystic fibrosis (CF) is a monogenic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, with lung and liver manifestations. Because of pitfalls of gene therapy, novel approaches for reconstitution of the airway epithelium and CFTR expression should be explored. In the present study, human amniotic mesenchymal stem cells (hAMSCs) were isolated from term placentas and characterized for expression of phenotypic and pluripotency markers, and for differentiation potential towards mesoderm (osteogenic and adipogenic) lineages. Moreover, hAMSCs were induced to differentiate into hepatocyte-like cells, as demonstrated by mixed function oxidase activity and expression of albumin, alpha1-antitrypsin, and CK19. We also investigated the CFTR expression in hAMSCs upon isolation and in coculture with CF airway epithelial cells. Freshly isolated hAMSCs displayed low levels of CFTR mRNA, which even decreased with culture passages. Following staining with the vital dye CM-DiI, hAMSCs were mixed with CFBE41o- respiratory epithelial cells and seeded onto permeable filters. Flow cytometry demonstrated that 33–50% of hAMSCs acquired a detectable CFTR expression on the apical membrane, a result confirmed by confocal microscopy. Our data show that amniotic MSCs have the potential to differentiate into epithelial cells of organs relevant in CF pathogenesis and may contribute to partial correction of the CF phenotype.
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spelling pubmed-32704332012-02-07 Amniotic Mesenchymal Stem Cells: A New Source for Hepatocyte-Like Cells and Induction of CFTR Expression by Coculture with Cystic Fibrosis Airway Epithelial Cells Paracchini, Valentina Carbone, Annalucia Colombo, Federico Castellani, Stefano Mazzucchelli, Silvia Di Gioia, Sante Degiorgio, Dario Seia, Manuela Porretti, Laura Colombo, Carla Conese, Massimo J Biomed Biotechnol Research Article Cystic fibrosis (CF) is a monogenic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, with lung and liver manifestations. Because of pitfalls of gene therapy, novel approaches for reconstitution of the airway epithelium and CFTR expression should be explored. In the present study, human amniotic mesenchymal stem cells (hAMSCs) were isolated from term placentas and characterized for expression of phenotypic and pluripotency markers, and for differentiation potential towards mesoderm (osteogenic and adipogenic) lineages. Moreover, hAMSCs were induced to differentiate into hepatocyte-like cells, as demonstrated by mixed function oxidase activity and expression of albumin, alpha1-antitrypsin, and CK19. We also investigated the CFTR expression in hAMSCs upon isolation and in coculture with CF airway epithelial cells. Freshly isolated hAMSCs displayed low levels of CFTR mRNA, which even decreased with culture passages. Following staining with the vital dye CM-DiI, hAMSCs were mixed with CFBE41o- respiratory epithelial cells and seeded onto permeable filters. Flow cytometry demonstrated that 33–50% of hAMSCs acquired a detectable CFTR expression on the apical membrane, a result confirmed by confocal microscopy. Our data show that amniotic MSCs have the potential to differentiate into epithelial cells of organs relevant in CF pathogenesis and may contribute to partial correction of the CF phenotype. Hindawi Publishing Corporation 2012 2012-01-22 /pmc/articles/PMC3270433/ /pubmed/22315512 http://dx.doi.org/10.1155/2012/575471 Text en Copyright © 2012 Valentina Paracchini et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Paracchini, Valentina
Carbone, Annalucia
Colombo, Federico
Castellani, Stefano
Mazzucchelli, Silvia
Di Gioia, Sante
Degiorgio, Dario
Seia, Manuela
Porretti, Laura
Colombo, Carla
Conese, Massimo
Amniotic Mesenchymal Stem Cells: A New Source for Hepatocyte-Like Cells and Induction of CFTR Expression by Coculture with Cystic Fibrosis Airway Epithelial Cells
title Amniotic Mesenchymal Stem Cells: A New Source for Hepatocyte-Like Cells and Induction of CFTR Expression by Coculture with Cystic Fibrosis Airway Epithelial Cells
title_full Amniotic Mesenchymal Stem Cells: A New Source for Hepatocyte-Like Cells and Induction of CFTR Expression by Coculture with Cystic Fibrosis Airway Epithelial Cells
title_fullStr Amniotic Mesenchymal Stem Cells: A New Source for Hepatocyte-Like Cells and Induction of CFTR Expression by Coculture with Cystic Fibrosis Airway Epithelial Cells
title_full_unstemmed Amniotic Mesenchymal Stem Cells: A New Source for Hepatocyte-Like Cells and Induction of CFTR Expression by Coculture with Cystic Fibrosis Airway Epithelial Cells
title_short Amniotic Mesenchymal Stem Cells: A New Source for Hepatocyte-Like Cells and Induction of CFTR Expression by Coculture with Cystic Fibrosis Airway Epithelial Cells
title_sort amniotic mesenchymal stem cells: a new source for hepatocyte-like cells and induction of cftr expression by coculture with cystic fibrosis airway epithelial cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3270433/
https://www.ncbi.nlm.nih.gov/pubmed/22315512
http://dx.doi.org/10.1155/2012/575471
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