title: Generation of stem cell-based bioartificial anterior cruciate ligament (ACL) grafts for effective ACL rupture repair.
abstract: 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 21days 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.
authors.affiliation: Department of Biomedical Research, Institute of Molecular Biology & Biotechnology, Foundation of Research and Technology-Hellas, University Campus, 45110 Ioannina, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Kouroupis
authors.affiliation: Department of Biomedical Research, Institute of Molecular Biology & Biotechnology, Foundation of Research and Technology-Hellas, University Campus, 45110 Ioannina, Greece.
authors.forename: Athena
authors.initials: A
authors.lastname: Kyrkou
authors.affiliation: Department of Pathology, University of Ioannina, 45110 Ioannina, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Triantafyllidi
authors.affiliation: Centre of Clinical, Experimental Surgery and Translational Research, Experimental Surgery Unit, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece; Attikon animal hospital, 19002, Paiania, Athens, Greece.
authors.forename: Michalis
authors.initials: M
authors.lastname: Katsimpoulas
authors.affiliation: Department of Biology, Electron microscopy laboratory, University of Crete, 70013 Heraklion, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Chalepakis
authors.affiliation: Department of Pathology, University of Ioannina, 45110 Ioannina, Greece.
authors.forename: Anna
authors.initials: A
authors.lastname: Goussia
authors.affiliation: Orthopaedic Sports Medicine Center-Department of Orthopaedic Surgery, University of Ioannina, 45110 Ioannina, Greece.
authors.forename: Anastasios
authors.initials: A
authors.lastname: Georgoulis
authors.affiliation: Department of Biomedical Research, Institute of Molecular Biology & Biotechnology, Foundation of Research and Technology-Hellas, University Campus, 45110 Ioannina, Greece; School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
authors.forename: Carol
authors.initials: C
authors.lastname: Murphy
authors.affiliation: Department of Biomedical Research, Institute of Molecular Biology & Biotechnology, Foundation of Research and Technology-Hellas, University Campus, 45110 Ioannina, Greece; School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK; Laboratory of Biological Chemistry, Medical School, University of Ioannina, 45110 Ioannina, Greece. Electronic address: thfotsis@uoi.gr.
authors.forename: Theodore
authors.initials: T
authors.lastname: Fotsis
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D016118:Anterior Cruciate Ligament / Q000000981:diagnostic imaging / Q000473:pathology; D000070598:Anterior Cruciate Ligament Injuries / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy* / Q000662:veterinary; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D065150:Cellular Reprogramming; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D052816:Foreskin / Q000166:cytology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D008297:Male; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D023421:Models, Animal; D000072078:Positron Emission Tomography Computed Tomography; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D013552:Swine
chemical_list: D055396:Bone Morphogenetic Protein 2; D016222:Fibroblast Growth Factor 2
keywords: Anterior cruciate ligament reconstruction; Bioartificial ACL graft; Biomaterials; Human adipose tissue multipotential stromal cells; Human induced pluripotent stem cells; Tissue engineering