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Expansion and Characterization of Neonatal Cardiac Pericytes Provides a Novel Cellular Option for Tissue Engineering in Congenital Heart Disease

BACKGROUND: Living grafts produced by combining autologous heart-resident stem/progenitor cells and tissue engineering could provide a new therapeutic option for definitive correction of congenital heart disease. The aim of the study was to investigate the antigenic profile, expansion/differentiatio...

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Autores principales: Avolio, Elisa, Rodriguez-Arabaolaza, Iker, Spencer, Helen L, Riu, Federica, Mangialardi, Giuseppe, Slater, Sadie C, Rowlinson, Jonathan, Alvino, Valeria V, Idowu, Oluwasomidotun O, Soyombo, Stephanie, Oikawa, Atsuhiko, Swim, Megan M, Kong, Cherrie H T, Cheng, Hongwei, Jia, Huidong, Ghorbel, Mohamed T, Hancox, Jules C, Orchard, Clive H, Angelini, Gianni, Emanueli, Costanza, Caputo, Massimo, Madeddu, Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599542/
https://www.ncbi.nlm.nih.gov/pubmed/26080813
http://dx.doi.org/10.1161/JAHA.115.002043
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author Avolio, Elisa
Rodriguez-Arabaolaza, Iker
Spencer, Helen L
Riu, Federica
Mangialardi, Giuseppe
Slater, Sadie C
Rowlinson, Jonathan
Alvino, Valeria V
Idowu, Oluwasomidotun O
Soyombo, Stephanie
Oikawa, Atsuhiko
Swim, Megan M
Kong, Cherrie H T
Cheng, Hongwei
Jia, Huidong
Ghorbel, Mohamed T
Hancox, Jules C
Orchard, Clive H
Angelini, Gianni
Emanueli, Costanza
Caputo, Massimo
Madeddu, Paolo
author_facet Avolio, Elisa
Rodriguez-Arabaolaza, Iker
Spencer, Helen L
Riu, Federica
Mangialardi, Giuseppe
Slater, Sadie C
Rowlinson, Jonathan
Alvino, Valeria V
Idowu, Oluwasomidotun O
Soyombo, Stephanie
Oikawa, Atsuhiko
Swim, Megan M
Kong, Cherrie H T
Cheng, Hongwei
Jia, Huidong
Ghorbel, Mohamed T
Hancox, Jules C
Orchard, Clive H
Angelini, Gianni
Emanueli, Costanza
Caputo, Massimo
Madeddu, Paolo
author_sort Avolio, Elisa
collection PubMed
description BACKGROUND: Living grafts produced by combining autologous heart-resident stem/progenitor cells and tissue engineering could provide a new therapeutic option for definitive correction of congenital heart disease. The aim of the study was to investigate the antigenic profile, expansion/differentiation capacity, paracrine activity, and pro-angiogenic potential of cardiac pericytes and to assess their engrafting capacity in clinically certified prosthetic grafts. METHODS AND RESULTS: CD34(pos) cells, negative for the endothelial markers CD31 and CD146, were identified by immunohistochemistry in cardiac leftovers from infants and children undergoing palliative repair of congenital cardiac defects. Following isolation by immunomagnetic bead-sorting and culture on plastic in EGM-2 medium supplemented with growth factors and serum, CD34(pos)/CD31(neg) cells gave rise to a clonogenic, highly proliferative (>20 million at P5), spindle-shape cell population. The following populations were shown to expresses pericyte/mesenchymal and stemness markers. After exposure to differentiation media, the expanded cardiac pericytes acquired markers of vascular smooth muscle cells, but failed to differentiate into endothelial cells or cardiomyocytes. However, in Matrigel, cardiac pericytes form networks and enhance the network capacity of endothelial cells. Moreover, they produce collagen-1 and release chemo-attractants that stimulate the migration of c-Kit(pos) cardiac stem cells. Cardiac pericytes were then seeded onto clinically approved xenograft scaffolds and cultured in a bioreactor. After 3 weeks, fluorescent microscopy showed that cardiac pericytes had penetrated into and colonized the graft. CONCLUSIONS: These findings open new avenues for cellular functionalization of prosthetic grafts to be applied in reconstructive surgery of congenital heart disease.
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spelling pubmed-45995422015-10-16 Expansion and Characterization of Neonatal Cardiac Pericytes Provides a Novel Cellular Option for Tissue Engineering in Congenital Heart Disease Avolio, Elisa Rodriguez-Arabaolaza, Iker Spencer, Helen L Riu, Federica Mangialardi, Giuseppe Slater, Sadie C Rowlinson, Jonathan Alvino, Valeria V Idowu, Oluwasomidotun O Soyombo, Stephanie Oikawa, Atsuhiko Swim, Megan M Kong, Cherrie H T Cheng, Hongwei Jia, Huidong Ghorbel, Mohamed T Hancox, Jules C Orchard, Clive H Angelini, Gianni Emanueli, Costanza Caputo, Massimo Madeddu, Paolo J Am Heart Assoc Original Research BACKGROUND: Living grafts produced by combining autologous heart-resident stem/progenitor cells and tissue engineering could provide a new therapeutic option for definitive correction of congenital heart disease. The aim of the study was to investigate the antigenic profile, expansion/differentiation capacity, paracrine activity, and pro-angiogenic potential of cardiac pericytes and to assess their engrafting capacity in clinically certified prosthetic grafts. METHODS AND RESULTS: CD34(pos) cells, negative for the endothelial markers CD31 and CD146, were identified by immunohistochemistry in cardiac leftovers from infants and children undergoing palliative repair of congenital cardiac defects. Following isolation by immunomagnetic bead-sorting and culture on plastic in EGM-2 medium supplemented with growth factors and serum, CD34(pos)/CD31(neg) cells gave rise to a clonogenic, highly proliferative (>20 million at P5), spindle-shape cell population. The following populations were shown to expresses pericyte/mesenchymal and stemness markers. After exposure to differentiation media, the expanded cardiac pericytes acquired markers of vascular smooth muscle cells, but failed to differentiate into endothelial cells or cardiomyocytes. However, in Matrigel, cardiac pericytes form networks and enhance the network capacity of endothelial cells. Moreover, they produce collagen-1 and release chemo-attractants that stimulate the migration of c-Kit(pos) cardiac stem cells. Cardiac pericytes were then seeded onto clinically approved xenograft scaffolds and cultured in a bioreactor. After 3 weeks, fluorescent microscopy showed that cardiac pericytes had penetrated into and colonized the graft. CONCLUSIONS: These findings open new avenues for cellular functionalization of prosthetic grafts to be applied in reconstructive surgery of congenital heart disease. John Wiley & Sons, Ltd 2015-06-16 /pmc/articles/PMC4599542/ /pubmed/26080813 http://dx.doi.org/10.1161/JAHA.115.002043 Text en © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. http://creativecommons.org/licenses/by-nc/4.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Research
Avolio, Elisa
Rodriguez-Arabaolaza, Iker
Spencer, Helen L
Riu, Federica
Mangialardi, Giuseppe
Slater, Sadie C
Rowlinson, Jonathan
Alvino, Valeria V
Idowu, Oluwasomidotun O
Soyombo, Stephanie
Oikawa, Atsuhiko
Swim, Megan M
Kong, Cherrie H T
Cheng, Hongwei
Jia, Huidong
Ghorbel, Mohamed T
Hancox, Jules C
Orchard, Clive H
Angelini, Gianni
Emanueli, Costanza
Caputo, Massimo
Madeddu, Paolo
Expansion and Characterization of Neonatal Cardiac Pericytes Provides a Novel Cellular Option for Tissue Engineering in Congenital Heart Disease
title Expansion and Characterization of Neonatal Cardiac Pericytes Provides a Novel Cellular Option for Tissue Engineering in Congenital Heart Disease
title_full Expansion and Characterization of Neonatal Cardiac Pericytes Provides a Novel Cellular Option for Tissue Engineering in Congenital Heart Disease
title_fullStr Expansion and Characterization of Neonatal Cardiac Pericytes Provides a Novel Cellular Option for Tissue Engineering in Congenital Heart Disease
title_full_unstemmed Expansion and Characterization of Neonatal Cardiac Pericytes Provides a Novel Cellular Option for Tissue Engineering in Congenital Heart Disease
title_short Expansion and Characterization of Neonatal Cardiac Pericytes Provides a Novel Cellular Option for Tissue Engineering in Congenital Heart Disease
title_sort expansion and characterization of neonatal cardiac pericytes provides a novel cellular option for tissue engineering in congenital heart disease
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599542/
https://www.ncbi.nlm.nih.gov/pubmed/26080813
http://dx.doi.org/10.1161/JAHA.115.002043
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