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Reconstruction of the pulmonary artery by a novel biodegradable conduit engineered with perinatal stem cell-derived vascular smooth muscle cells enables physiological vascular growth in a large animal model of congenital heart disease

Lack of growth potential of available grafts represents a bottleneck in the correction of congenital heart defects. Here we used a swine small intestinal submucosa (SIS) graft functionalized with mesenchymal stem cell (MSC)-derived vascular smooth muscle cells (VSMCs), for replacement of the pulmona...

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Autores principales: Ghorbel, Mohamed T., Jia, Huidong, Swim, Megan M., Iacobazzi, Dominga, Albertario, Ambra, Zebele, Carlo, Holopherne-Doran, Delphine, Hollander, Anthony, Madeddu, Paolo, Caputo, Massimo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658806/
https://www.ncbi.nlm.nih.gov/pubmed/31255979
http://dx.doi.org/10.1016/j.biomaterials.2019.119284
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author Ghorbel, Mohamed T.
Jia, Huidong
Swim, Megan M.
Iacobazzi, Dominga
Albertario, Ambra
Zebele, Carlo
Holopherne-Doran, Delphine
Hollander, Anthony
Madeddu, Paolo
Caputo, Massimo
author_facet Ghorbel, Mohamed T.
Jia, Huidong
Swim, Megan M.
Iacobazzi, Dominga
Albertario, Ambra
Zebele, Carlo
Holopherne-Doran, Delphine
Hollander, Anthony
Madeddu, Paolo
Caputo, Massimo
author_sort Ghorbel, Mohamed T.
collection PubMed
description Lack of growth potential of available grafts represents a bottleneck in the correction of congenital heart defects. Here we used a swine small intestinal submucosa (SIS) graft functionalized with mesenchymal stem cell (MSC)-derived vascular smooth muscle cells (VSMCs), for replacement of the pulmonary artery in piglets. MSCs were expanded from human umbilical cord blood or new-born swine peripheral blood, seeded onto decellularized SIS grafts and conditioned in a bioreactor to differentiate into VSMCs. Results indicate the equivalence of generating grafts engineered with human or swine MSC-derived VSMCs. Next, we conducted a randomized, controlled study in piglets (12–15 kg), which had the left pulmonary artery reconstructed with swine VSMC-engineered or acellular conduit grafts. Piglets recovered well from surgery, with no casualty and similar growth rate in either group. After 6 months, grafted arteries had larger circumference in the cellular group (28.3 ± 2.3 vs 18.3 ± 2.1 mm, P < 0.001), but without evidence of aneurism formation. Immunohistochemistry showed engineered grafts were composed of homogeneous endothelium covered by multi-layered muscular media, whereas the acellular grafts exhibited a patchy endothelial cell layer and a thinner muscular layer. RESULTS: show the feasibility and efficacy of pulmonary artery reconstruction using clinically available grafts engineered with allogeneic VSMCs in growing swine.
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spelling pubmed-66588062019-10-01 Reconstruction of the pulmonary artery by a novel biodegradable conduit engineered with perinatal stem cell-derived vascular smooth muscle cells enables physiological vascular growth in a large animal model of congenital heart disease Ghorbel, Mohamed T. Jia, Huidong Swim, Megan M. Iacobazzi, Dominga Albertario, Ambra Zebele, Carlo Holopherne-Doran, Delphine Hollander, Anthony Madeddu, Paolo Caputo, Massimo Biomaterials Article Lack of growth potential of available grafts represents a bottleneck in the correction of congenital heart defects. Here we used a swine small intestinal submucosa (SIS) graft functionalized with mesenchymal stem cell (MSC)-derived vascular smooth muscle cells (VSMCs), for replacement of the pulmonary artery in piglets. MSCs were expanded from human umbilical cord blood or new-born swine peripheral blood, seeded onto decellularized SIS grafts and conditioned in a bioreactor to differentiate into VSMCs. Results indicate the equivalence of generating grafts engineered with human or swine MSC-derived VSMCs. Next, we conducted a randomized, controlled study in piglets (12–15 kg), which had the left pulmonary artery reconstructed with swine VSMC-engineered or acellular conduit grafts. Piglets recovered well from surgery, with no casualty and similar growth rate in either group. After 6 months, grafted arteries had larger circumference in the cellular group (28.3 ± 2.3 vs 18.3 ± 2.1 mm, P < 0.001), but without evidence of aneurism formation. Immunohistochemistry showed engineered grafts were composed of homogeneous endothelium covered by multi-layered muscular media, whereas the acellular grafts exhibited a patchy endothelial cell layer and a thinner muscular layer. RESULTS: show the feasibility and efficacy of pulmonary artery reconstruction using clinically available grafts engineered with allogeneic VSMCs in growing swine. Elsevier Science 2019-10 /pmc/articles/PMC6658806/ /pubmed/31255979 http://dx.doi.org/10.1016/j.biomaterials.2019.119284 Text en © 2019 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ghorbel, Mohamed T.
Jia, Huidong
Swim, Megan M.
Iacobazzi, Dominga
Albertario, Ambra
Zebele, Carlo
Holopherne-Doran, Delphine
Hollander, Anthony
Madeddu, Paolo
Caputo, Massimo
Reconstruction of the pulmonary artery by a novel biodegradable conduit engineered with perinatal stem cell-derived vascular smooth muscle cells enables physiological vascular growth in a large animal model of congenital heart disease
title Reconstruction of the pulmonary artery by a novel biodegradable conduit engineered with perinatal stem cell-derived vascular smooth muscle cells enables physiological vascular growth in a large animal model of congenital heart disease
title_full Reconstruction of the pulmonary artery by a novel biodegradable conduit engineered with perinatal stem cell-derived vascular smooth muscle cells enables physiological vascular growth in a large animal model of congenital heart disease
title_fullStr Reconstruction of the pulmonary artery by a novel biodegradable conduit engineered with perinatal stem cell-derived vascular smooth muscle cells enables physiological vascular growth in a large animal model of congenital heart disease
title_full_unstemmed Reconstruction of the pulmonary artery by a novel biodegradable conduit engineered with perinatal stem cell-derived vascular smooth muscle cells enables physiological vascular growth in a large animal model of congenital heart disease
title_short Reconstruction of the pulmonary artery by a novel biodegradable conduit engineered with perinatal stem cell-derived vascular smooth muscle cells enables physiological vascular growth in a large animal model of congenital heart disease
title_sort reconstruction of the pulmonary artery by a novel biodegradable conduit engineered with perinatal stem cell-derived vascular smooth muscle cells enables physiological vascular growth in a large animal model of congenital heart disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658806/
https://www.ncbi.nlm.nih.gov/pubmed/31255979
http://dx.doi.org/10.1016/j.biomaterials.2019.119284
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