Impact of an autologous oxygenating matrix culture system on rat islet transplantation outcome |
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| Affiliation: | 1. UMR DIATHEC, EA 7294, Centre Européen d’Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Bld René Leriche, Strasbourg, France;2. Structure d’Endocrinologie, Diabète-Nutrition et Addictologie, Pôle NUDE, Hôpitaux Universitaires de Strasbourg, Strasbourg, France;3. Department of Vascular Surgery, John Radcliffe Hospital, Oxford, United Kingdom;4. Service de chirurgie Plastique et maxillo faciale, Hôpitaux Universitaires de Strasbourg, Strasbourg, France;1. Department of Renal Transplantation, Hospital of Nephrology, the First Affiliated Hospital, Medical College, Xi''an Jiaotong University, Xi''an City, Shannxi Province, People''s Republic of China;2. Department of Rheumatism and Immunology, the First Affiliated Hospital, Medical College, Xi''an Jiaotong University, Xi''an City, Shannxi Province, People''s Republic of China;3. Department of Hepatobiliary, the First Affiliated Hospital, Medical College, Xi''an Jiaotong University, Xi''an City, Shannxi Province, People''s Republic of China;4. Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada;1. Center for Regenerative Medicine, Massachusetts General Hospital, United States;2. Harvard Medical School, United States;3. Division of Thoracic Surgery, Department of Surgery, Massachusetts General Hospital, United States;4. Harvard Stem Cell Institute, United States;1. Institute for Advancing Translational Medicine in Bone & Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China;2. Academician Chen Xinzi Workroom for Advancing Translational Medicine in Bone & Joint Diseases, Kunshan RNAi Institute, Kunshan Industrial Technology Research Institute, Kunshan, Jiangsu 215347, China;3. Institute of Integrated Bioinformatic Medicine and Translational Sciences, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen 518057, China;4. Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen 518057, China;5. Hong Kong Baptist University – Northwestern Polytechnical University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space, Shenzhen, 518057, China;6. Key Laboratory for Space Bioscience and Biotechnology, Institute of Special Environmental Biophysics, School of Life Science, Northwestern Polytechnical University, Xi''an, 721000, China;7. Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China;8. Department of Biology and Chemistry, City University of Hong Kong, 999077, Hong Kong, China;9. School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China;10. Department of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi''an, 710032, China;11. Department of Orthopaedics & Traumatology, Shenzhen People''s Hospital, Second Medical College of Ji''nan University, Shenzhen, 518020, China;12. Molecular Lab, School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, WA 6009, Australia;13. Department of Chemistry, University of Florida, Gainesville, FA 32611-7200, USA;14. Department of Physiology and Functional Genomics, University of Florida, Gainesville, FA 32611-7200, USA;15. Center for Research at Bio/Nano Interface, Shands Cancer Center, University of Florida, Gainesville, FA 32611-7200, USA;p. Institute of Molecular Medicine, Peking University, Beijing, 100871, China |
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| Abstract: | Disruption of the pancreatic islet environment combined with the decrease in oxygen supply that occurs during isolation leads to poor islet survival. The aim of this study was to validate the benefit of using a plasma-based scaffold supplemented with perfluorodecalin to improve islet transplantation outcome.Rat islets were cultured in three conditions: i) control group, ii) plasma based-matrix (P-matrix), and iii) P-matrix supplemented with emulsified perfluorodecalin. After 24 h culture, matrix/cell contacts (Integrinβ1, p-FAK/FAK, p-Akt/Akt), survival (caspase 3, TUNEL, FDA/PI), function, and HIF-1α translocation were assessed. Afterwards, P-matrices were dissolved and the islets were intraportally transplanted. Graft function was monitored for 31 days with glycaemia and C-peptide follow up. Inflammation was assessed by histology (macrophage and granulocyte staining) and thrombin/anti-thrombin complex measurement.Islet survival correlated with an increase in integrin, FAK, and Akt activation in P-matrices and function was maintained. Perfluorodecalin supplementation decreased translocation of HIF-1α in the nucleus and post-transplantation islet structure was better preserved in P-matrices, but a quicker activation of IBMIR resulted in early loss of graft function.“Oxygenating” P-matrices provided a real benefit to islet survival and resistance in vivo. However, intraportal transplantation is not suitable for this kind of culture due to IBMIR; thus, alternative sites must be explored. |
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