In vitro fabrication of autologous living tissue‐engineered vascular grafts based on prenatally harvested ovine amniotic fluid‐derived stem cells |
| |
| Authors: | Benedikt Weber Debora Kehl Ulrich Bleul Luc Behr Sébastien Sammut Laura Frese Agnieszka Ksiazek Josef Achermann Gerald Stranzinger Jérôme Robert Bart Sanders Michele Sidler Chad E. Brokopp Steven T. Proulx Thomas Frauenfelder Roman Schoenauer Maximilian Y. Emmert Volkmar Falk Simon P. Hoerstrup |
| |
| Affiliation: | 1. Swiss Centre for Regenerative Medicine, University of Zurich, Zurich, Switzerland;2. Clinic for Cardiovascular Surgery and Department of Surgical Research, University Hospital of Zurich, Zurich, Switzerland;3. Clinic of Reproductive Medicine, Department of Food Animals, Vetsuisse‐Faculty University of Zurich, Zurich, Switzerland;4. IMM Recherche, Institute Mutualiste Montsouris, Paris, France;5. Human Genetics Laboratory, Genetica AG, Zurich, Switzerland;6. Breeding Biology Group, Swiss Federal Institute of Technology, Zurich, Switzerland;7. Institute of Clinical Chemistry, University Hospital Zurich, Zurich, Switzerland;8. Department of Biomedical Engineering, Soft Tissue Biomechanics and Tissue Engineering, Eindhoven University of Technology, the Netherlands;9. Musculo‐sceletal Research Unit, Vetsuisse‐Faculty, University of Zurich, Zurich, Switzerland;10. Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Switzerland;11. Department of Diagnostic Radiology, University Hospital Zurich, Zurich, Switzerland;12. Centre for Applied Biotechnology and Molecular Medicine (CABMM), Zurich, Switzerland |
| |
| Abstract: | Amniotic fluid cells (AFCs) have been proposed as a valuable source for tissue engineering and regenerative medicine. However, before clinical implementation, rigorous evaluation of this cell source in clinically relevant animal models accepted by regulatory authorities is indispensable. Today, the ovine model represents one of the most accepted preclinical animal models, in particular for cardiovascular applications. Here, we investigate the isolation and use of autologous ovine AFCs as cell source for cardiovascular tissue engineering applications. Fetal fluids were aspirated in vivo from pregnant ewes (n = 9) and from explanted uteri post mortem at different gestational ages (n = 91). Amniotic non‐allantoic fluid nature was evaluated biochemically and in vivo samples were compared with post mortem reference samples. Isolated cells revealed an immunohistochemical phenotype similar to ovine bone marrow‐derived mesenchymal stem cells (MSCs) and showed expression of stem cell factors described for embryonic stem cells, such as NANOG and STAT‐3. Isolated ovine amniotic fluid‐derived MSCs were screened for numeric chromosomal aberrations and successfully differentiated into several mesodermal phenotypes. Myofibroblastic ovine AFC lineages were then successfully used for the in vitro fabrication of small‐ and large‐diameter tissue‐engineered vascular grafts (n = 10) and cardiovascular patches (n = 34), laying the foundation for the use of this relevant pre‐clinical in vivo assessment model for future amniotic fluid cell‐based therapeutic applications. Copyright © 2013 John Wiley & Sons, Ltd. |
| |
| Keywords: | amniotic fluid mesenchymal stem cells cardiovascular tissue engineering ovine in‐vivo model fetal model vascular graft |
|
|
