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, MT, Jia, H, Swim, MM, Iacobazzi, D, Albertario, A, Zebele, C, Holopherne-Doran, D, Hollander, A ORCID: 0000-0003-2897-3747, Madeddu, P and Caputo, M
(2019) 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. Biomaterials, 217.

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Abstract

© 2019 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.

Item Type: Article
Uncontrolled Keywords: congenital heart disease, stem cells, tissue-engineering, grafts
Depositing User: Symplectic Admin
Date Deposited: 11 Jul 2019 15:40
Last Modified: 20 Oct 2021 21:13
DOI: 10.1016/j.biomaterials.2019.119284
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3049530