A double-chamber rotating bioreactor for the development of tissue-engineered hollow organs: From concept to clinical trial |
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| Authors: | M. Adelaide Asnaghi Philipp Jungebluth Manuela T. Raimondi Sally C. Dickinson Louisa E.N. Rees Tetsuhiko Go Tristan A. Cogan Amanda Dodson Pier Paolo Parnigotto Anthony P. Hollander Martin A. Birchall Maria Teresa Conconi Paolo Macchiarini Sara Mantero |
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| Affiliation: | 1. Department of Bioengineering, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milan, Italy;2. Department of General Thoracic Surgery, Hospital Clinic de Barcelona, University of Barcelona, c Villarroel 170, E-08036 Barcelona, Spain;3. LaBS, Department of Structural Engineering, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milan, Italy;4. IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161 Milan, Italy;5. Department of Cellular and Molecular Medicine, University of Bristol, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK;6. School of Clinical Veterinary Science, University of Bristol, Langford, Bristol BS40 5DU, UK;7. Department of Pharmaceutical Sciences, University of Padua, Via F. Marzolo 5, 35131 Padua, Italy;8. Department of Clinical Medicine at South Bristol, Faculty of Medicine and Dentistry, University of Bristol, Bristol, UK;1. Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk, 790-784, South Korea;2. Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157, USA;3. Division of Otolaryngology and HNS, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 137-701, South Korea;4. Biomaterials Research Center, Korea Institute of Science and Technology, 5 Hwarang-ro 14-gil, Seongbuk-gu, Seoul, 136-791, South Korea;1. Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106, USA;2. Department of Biomedical Engineering, Worcester Polytechnic Institute, 100 Institute Rd., Worcester, MA 01609, USA;3. Department of Orthopaedic Surgery, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106, USA;1. Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Spain;2. Master''s and Doctoral Degree Programs in Rehabilitation Sciences, Nove de Julho University, Sao Paulo, Brazil;3. CIBER de Enfermedades Respiratorias, Bunyola, Spain;4. Institut de Bioenginyeria de Catalunya, Barcelona, Spain;1. Department of Plastic and Reconstructive Surgery, Shanghai 9th People''s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, Shanghai Stem Cell Institute, Shanghai, PR China;2. National Tissue Engineering Center of China, Shanghai, PR China;1. The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA;2. Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, South Korea;3. Department of Otolaryngology and HNS, College of Medicine, The Catholic University of Korea, Seoul, South Korea;4. Veterinary Medical Center, Chungbuk National University, Cheongju, South Korea;5. Department of Biomedical Science, College of Medicine, The Catholic University of Korea, Seoul, South Korea;1. Surgery Unit, UCL Institute of Child Health and Great Ormond Street Hospital, 30 Guilford Street, London WC1N 1EH, UK;2. Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA;3. Neural Development Unit, UCL Institute of Child Health, London WC1N 1EH, UK;4. Department of Information Engineering, University of Padua, Italy;5. Department of Histopathology, UCL Institute of Child Health and Great Ormond Street Hospital, London WC1N 1EH, UK;6. Division of Bioscience, University College London, London WC1N 1EH, UK;7. McGowan Institute for Regenerative Medicine, Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA;8. Department of Pediatrics, Children''s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA;9. UCL Ear Institute, London WC1X 8EE, UK;10. Department of Cardiothoracic Surgery, Great Ormond Street Hospital, London WC1N 3JH, UK;11. Department of Cardiothoracic Surgery, Children''s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA |
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| Abstract: | Cell and tissue engineering are now being translated into clinical organ replacement, offering alternatives to fight morbidity, organ shortages and ethico-social problems associated with allotransplantation. Central to the recent first successful use of stem cells to create an organ replacement in man was our development of a bioreactor environment. Critical design features were the abilities to drive the growth of two different cell types, to support 3D maturation, to maintain biomechanical and biological properties and to provide appropriate hydrodynamic stimuli and adequate mass transport. An analytical model was developed and applied to predict oxygen profiles in the bioreactor-cultured organ construct and in the culture media, comparing representative culture configurations and operating conditions. Autologous respiratory epithelial cells and mesenchymal stem cells (BMSCs, then differentiated into chondrocytes) were isolated, characterized and expanded. Both cell types were seeded and cultured onto a decellularized human donor tracheal matrix within the bioreactor. One year post-operatively, graft and patient are healthy, and biopsies confirm angiogenesis, viable epithelial cells and chondrocytes. Our rotating double-chamber bioreactor permits the efficient repopulation of a decellularized human matrix, a concept that can be applied clinically, as demonstrated by the successful tracheal transplantation. |
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| Keywords: | Bioreactor Tissue engineering Co-culture Oxygenation Stem cells Airway transplantation |
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