Generation of stem cell-based bioartificial anterior cruciate ligament (ACL) grafts for effective ACL rupture repair

Dimitrios Kouroupis; Athena Kyrkou; Eleni Triantafyllidi; Michalis Katsimpoulas; George Chalepakis; Anna Goussia; Anastasios Georgoulis; Carol Murphy; Theodore Fotsis

doi:10.1016/j.scr.2016.04.016

Stem Cell Research (Sep 2016)

Generation of stem cell-based bioartificial anterior cruciate ligament (ACL) grafts for effective ACL rupture repair

Dimitrios Kouroupis,
Athena Kyrkou,
Eleni Triantafyllidi,
Michalis Katsimpoulas,
George Chalepakis,
Anna Goussia,
Anastasios Georgoulis,
Carol Murphy,
Theodore Fotsis

Affiliations

Dimitrios Kouroupis: Department of Biomedical Research, Institute of Molecular Biology & Biotechnology, Foundation of Research and Technology-Hellas, University Campus, 45110 Ioannina, Greece
Athena Kyrkou: Department of Biomedical Research, Institute of Molecular Biology & Biotechnology, Foundation of Research and Technology-Hellas, University Campus, 45110 Ioannina, Greece
Eleni Triantafyllidi: Department of Pathology, University of Ioannina, 45110 Ioannina, Greece
Michalis Katsimpoulas: Centre of Clinical, Experimental Surgery and Translational Research, Experimental Surgery Unit, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece
George Chalepakis: Department of Biology, Electron microscopy laboratory, University of Crete, 70013 Heraklion, Greece
Anna Goussia: Department of Pathology, University of Ioannina, 45110 Ioannina, Greece
Anastasios Georgoulis: Orthopaedic Sports Medicine Center-Department of Orthopaedic Surgery, University of Ioannina, 45110 Ioannina, Greece
Carol Murphy: Department of Biomedical Research, Institute of Molecular Biology & Biotechnology, Foundation of Research and Technology-Hellas, University Campus, 45110 Ioannina, Greece
Theodore Fotsis: Department of Biomedical Research, Institute of Molecular Biology & Biotechnology, Foundation of Research and Technology-Hellas, University Campus, 45110 Ioannina, Greece

DOI: https://doi.org/10.1016/j.scr.2016.04.016
Journal volume & issue: Vol. 17, no. 2
pp. 448 – 457

Abstract

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In the present study, we combined stem cell technology with a non-absorbable biomaterial for the reconstruction of the ruptured ACL. Towards this purpose, multipotential stromal cells derived either from subcutaneous human adipose tissue (hAT-MSCs) or from induced pluripotent stem cells (iPSCs) generated from human foreskin fibroblasts (hiPSC-MSCs) were cultured on the biomaterial for 21 days in vitro to generate a 3D bioartifical ACL graft. Stem cell differentiation towards bone and ligament at the ends and central part of the biomaterial was selectively induced using either BMP-2/FGF-2 or TGF-β/FGF-2 combinations, respectively. The bioartificial ACL graft was subsequently implanted in a swine ACL rupture model in place of the surgically removed normal ACL. Four months post-implantation, the tissue engineered ACL graft generated an ACL-like tissue exhibiting morphological and biochemical characteristics resembling those of normal ACL.

Published in Stem Cell Research

ISSN: 1873-5061 (Print); 1876-7753 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: https://www.journals.elsevier.com/stem-cell-research

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