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Reconstruction of the Swine Pulmonary Artery Using a Graft Engineered With Syngeneic Cardiac Pericytes

The neonatal heart represents an attractive source of regenerative cells. Here, we report the results of a randomized, controlled, investigator-blinded preclinical study, which assessed the safety and effectiveness of a matrix graft cellularized with cardiac pericytes (CPs) in a piglet model of pulm...

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Autores principales: Alvino, Valeria Vincenza, Thomas, Anita C., Ghorbel, Mohamed T., Rapetto, Filippo, Narayan, Srinivas A., Kilcooley, Michael, Iacobazzi, Dominga, Carrabba, Michele, Fagnano, Marco, Cathery, William, Avolio, Elisa, Caputo, Massimo, Madeddu, Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459923/
https://www.ncbi.nlm.nih.gov/pubmed/34568300
http://dx.doi.org/10.3389/fbioe.2021.715717
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author Alvino, Valeria Vincenza
Thomas, Anita C.
Ghorbel, Mohamed T.
Rapetto, Filippo
Narayan, Srinivas A.
Kilcooley, Michael
Iacobazzi, Dominga
Carrabba, Michele
Fagnano, Marco
Cathery, William
Avolio, Elisa
Caputo, Massimo
Madeddu, Paolo
author_facet Alvino, Valeria Vincenza
Thomas, Anita C.
Ghorbel, Mohamed T.
Rapetto, Filippo
Narayan, Srinivas A.
Kilcooley, Michael
Iacobazzi, Dominga
Carrabba, Michele
Fagnano, Marco
Cathery, William
Avolio, Elisa
Caputo, Massimo
Madeddu, Paolo
author_sort Alvino, Valeria Vincenza
collection PubMed
description The neonatal heart represents an attractive source of regenerative cells. Here, we report the results of a randomized, controlled, investigator-blinded preclinical study, which assessed the safety and effectiveness of a matrix graft cellularized with cardiac pericytes (CPs) in a piglet model of pulmonary artery (PA) reconstruction. Within each of five trios formed by 4-week-old female littermate piglets, one element (the donor) was sacrificed to provide a source of CPs, while the other two elements (the graft recipients) were allowed to reach the age of 10 weeks. During this time interval, culture-expanded donor CPs were seeded onto swine small intestinal submucosa (SIS) grafts, which were then shaped into conduits and conditioned in a flow bioreactor. Control unseeded SIS conduits were subjected to the same procedure. Then, recipient piglets were randomized to surgical reconstruction of the left PA (LPA) with unseeded or CP-seeded SIS conduits. Doppler echocardiography and cardiac magnetic resonance imaging (CMRI) were performed at baseline and 4-months post-implantation. Vascular explants were examined using histology and immunohistochemistry. All animals completed the scheduled follow-up. No group difference was observed in baseline imaging data. The final Doppler assessment showed that the LPA’s blood flow velocity was similar in the treatment groups. CMRI revealed a mismatch in the average growth of the grafted LPA and contralateral branch in both treatment groups. Histology of explanted arteries demonstrated that the CP-seeded grafts had a thicker luminal cell layer, more intraparietal arterioles, and a higher expression of endothelial nitric oxide synthase (eNOS) compared with unseeded grafts. Moreover, the LPA stump adjacent to the seeded graft contained more elastin and less collagen than the unseeded control. Syngeneic CP engineering did not accomplish the primary goal of supporting the graft’s growth but was able to improve secondary outcomes, such as the luminal cellularization and intraparietal vascularization of the graft, and elastic remodeling of the recipient artery. The beneficial properties of neonatal CPs may be considered in future bioengineering applications aiming to reproduce the cellular composition of native arteries.
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spelling pubmed-84599232021-09-24 Reconstruction of the Swine Pulmonary Artery Using a Graft Engineered With Syngeneic Cardiac Pericytes Alvino, Valeria Vincenza Thomas, Anita C. Ghorbel, Mohamed T. Rapetto, Filippo Narayan, Srinivas A. Kilcooley, Michael Iacobazzi, Dominga Carrabba, Michele Fagnano, Marco Cathery, William Avolio, Elisa Caputo, Massimo Madeddu, Paolo Front Bioeng Biotechnol Bioengineering and Biotechnology The neonatal heart represents an attractive source of regenerative cells. Here, we report the results of a randomized, controlled, investigator-blinded preclinical study, which assessed the safety and effectiveness of a matrix graft cellularized with cardiac pericytes (CPs) in a piglet model of pulmonary artery (PA) reconstruction. Within each of five trios formed by 4-week-old female littermate piglets, one element (the donor) was sacrificed to provide a source of CPs, while the other two elements (the graft recipients) were allowed to reach the age of 10 weeks. During this time interval, culture-expanded donor CPs were seeded onto swine small intestinal submucosa (SIS) grafts, which were then shaped into conduits and conditioned in a flow bioreactor. Control unseeded SIS conduits were subjected to the same procedure. Then, recipient piglets were randomized to surgical reconstruction of the left PA (LPA) with unseeded or CP-seeded SIS conduits. Doppler echocardiography and cardiac magnetic resonance imaging (CMRI) were performed at baseline and 4-months post-implantation. Vascular explants were examined using histology and immunohistochemistry. All animals completed the scheduled follow-up. No group difference was observed in baseline imaging data. The final Doppler assessment showed that the LPA’s blood flow velocity was similar in the treatment groups. CMRI revealed a mismatch in the average growth of the grafted LPA and contralateral branch in both treatment groups. Histology of explanted arteries demonstrated that the CP-seeded grafts had a thicker luminal cell layer, more intraparietal arterioles, and a higher expression of endothelial nitric oxide synthase (eNOS) compared with unseeded grafts. Moreover, the LPA stump adjacent to the seeded graft contained more elastin and less collagen than the unseeded control. Syngeneic CP engineering did not accomplish the primary goal of supporting the graft’s growth but was able to improve secondary outcomes, such as the luminal cellularization and intraparietal vascularization of the graft, and elastic remodeling of the recipient artery. The beneficial properties of neonatal CPs may be considered in future bioengineering applications aiming to reproduce the cellular composition of native arteries. Frontiers Media S.A. 2021-09-09 /pmc/articles/PMC8459923/ /pubmed/34568300 http://dx.doi.org/10.3389/fbioe.2021.715717 Text en Copyright © 2021 Alvino, Thomas, Ghorbel, Rapetto, Narayan, Kilcooley, Iacobazzi, Carrabba, Fagnano, Cathery, Avolio, Caputo and Madeddu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Alvino, Valeria Vincenza
Thomas, Anita C.
Ghorbel, Mohamed T.
Rapetto, Filippo
Narayan, Srinivas A.
Kilcooley, Michael
Iacobazzi, Dominga
Carrabba, Michele
Fagnano, Marco
Cathery, William
Avolio, Elisa
Caputo, Massimo
Madeddu, Paolo
Reconstruction of the Swine Pulmonary Artery Using a Graft Engineered With Syngeneic Cardiac Pericytes
title Reconstruction of the Swine Pulmonary Artery Using a Graft Engineered With Syngeneic Cardiac Pericytes
title_full Reconstruction of the Swine Pulmonary Artery Using a Graft Engineered With Syngeneic Cardiac Pericytes
title_fullStr Reconstruction of the Swine Pulmonary Artery Using a Graft Engineered With Syngeneic Cardiac Pericytes
title_full_unstemmed Reconstruction of the Swine Pulmonary Artery Using a Graft Engineered With Syngeneic Cardiac Pericytes
title_short Reconstruction of the Swine Pulmonary Artery Using a Graft Engineered With Syngeneic Cardiac Pericytes
title_sort reconstruction of the swine pulmonary artery using a graft engineered with syngeneic cardiac pericytes
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459923/
https://www.ncbi.nlm.nih.gov/pubmed/34568300
http://dx.doi.org/10.3389/fbioe.2021.715717
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