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

Mohamed T. Ghorbel, Huidong Jia, Megan M. Swim, Dominga Iacobazzi, Ambra Albertario, Carlo Zebele, Delphine Holopherne-Doran, Anthony Hollander, Paolo Madeddu, Massimo Caputo*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

2 Citations (Scopus)
229 Downloads (Pure)

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.

Original languageEnglish
Article number119284
Number of pages12
JournalBiomaterials
Volume217
Early online date20 Jun 2019
DOIs
Publication statusPublished - 1 Oct 2019

Bibliographical note

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

Keywords

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

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