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

Research output: Contribution to journalArticle

Authors

  • Dimitrios Kouroupis
  • Athena Kyrkou
  • Eleni Triantafyllidi
  • Michalis Katsimpoulas
  • George Chapelakis
  • Anna Goussia
  • Anastasios Georgoulis
  • Theodore Fotsis

Colleges, School and Institutes

External organisations

  • 1. Department of Biomedical Research, Institute of Molecular Biology & Biotechnology, Foundation of Research and Technology-Hellas, University Campus, 45110 Ioannina, Greece
  • Department of Pathology, University of Ioannina, 45110 Ioannina, Greece
  • Centre of Clinical, Experimental Surgery and Translational Research, Experimental Surgery Unit, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece and 4. Attikon animal hospital, 19002 Paiania, Athens, Greece
  • 5. Department of Biology, Electron microscopy laboratory, University of Crete, 70013 Heraklio, Greece
  • 6. Orthopaedic Sports Medicine Center-Department of Orthopaedic Surgery, University of Ioannina, 45110 Ioannina, Greece

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 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.

Details

Original languageEnglish
JournalStem Cell Research
Early online date22 Apr 2016
Publication statusE-pub ahead of print - 22 Apr 2016

Keywords

  • human induced pluripotent stem cells, bioartificial ACL graft, tissue engineering, biomaterials, Anterior cruciate ligament reconstruction, Human adipose tissue multipotential stromal cells