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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

Research output: Contribution to journalArticle

Original languageEnglish
Article number119284
Number of pages12
JournalBiomaterials
Volume217
Early online date20 Jun 2019
DOIs
DateAccepted/In press - 13 Jun 2019
DateE-pub ahead of print - 20 Jun 2019
DatePublished (current) - 1 Oct 2019

Abstract

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.

Additional information

Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.

    Research areas

  • Congenital heart disease, Grafts, Stem cells, Tissue-engineering

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via Elsevier at https://doi.org/10.1016/j.biomaterials.2019.119284 . Please refer to any applicable terms of use of the publisher.

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