Engineering an endothelialized, endocrine Neo-Pancreas: Evaluation of islet functionality in an ex vivo model.

Autor: Everwien H; Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Experimental Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany; Berlin Institute of Health (BIH), Anna-Louisa-Karsch-Str. 2, 10178 Berlin, Germany., Keshi E; Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Experimental Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany., Hillebrandt KH; Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Experimental Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany; Berlin Institute of Health (BIH), Anna-Louisa-Karsch-Str. 2, 10178 Berlin, Germany., Ludwig B; Medical Clinic III, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden University Hospital Carl Gustav Carus, Dresden, Germany., Weinhart M; Institute of Chemistry and Biochemistry, Germany and Institute of Physical Chemistry and Electrochemistry, Freie Universität Berlin, 30167 Hannover, Germany; Cluster of Excellence Matters of Activity, Image Space Material funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany´s Excellence Strategy - EXC 2025 - 390648296, Germany., Tang P; Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Experimental Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany., Beierle AS; Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Experimental Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany., Napierala H; Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Experimental Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany., Gassner JM; Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Experimental Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany., Seiffert N; Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Experimental Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany., Moosburner S; Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Experimental Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany., Geisel D; Department of Radiology, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany., Reutzel-Selke A; Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Experimental Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany., Strücker B; Berlin Institute of Health (BIH), Anna-Louisa-Karsch-Str. 2, 10178 Berlin, Germany; Department of General, Visceral and Transplant Surgery, Universitätsklinikum Münster, Münster, Germany., Pratschke J; Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Experimental Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany; Cluster of Excellence Matters of Activity, Image Space Material funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany´s Excellence Strategy - EXC 2025 - 390648296, Germany., Haep N; Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Experimental Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany; Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Sauer IM; Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Experimental Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany; Cluster of Excellence Matters of Activity, Image Space Material funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany´s Excellence Strategy - EXC 2025 - 390648296, Germany. Electronic address: igor.sauer@charite.de.
Jazyk: angličtina
Zdroj: Acta biomaterialia [Acta Biomater] 2020 Nov; Vol. 117, pp. 213-225. Date of Electronic Publication: 2020 Sep 16.
DOI: 10.1016/j.actbio.2020.09.022
Abstrakt: Islet-based recellularization of decellularized, repurposed rat livers may form a transplantable Neo-Pancreas. The aim of this study is the establishment of the necessary protocols, the evaluation of the organ structure and the analysis of the islet functionality ex vivo. After perfusion-based decellularization of rat livers, matrices were repopulated with endothelial cells and mesenchymal stromal cells, incubated for 8 days in a perfusion chamber, and finally repopulated on day 9 with intact rodent islets. Integrity and quality of re-endothelialization was assessed by histology and FITC-dextran perfusion assay. Functionality of the islets of Langerhans was determined on day 10 and day 12 via glucose stimulated insulin secretion. Blood gas analysis variables confirmed the stability of the perfusion cultivation. Histological staining showed that cells formed a monolayer inside the intact vascular structure. These findings were confirmed by electron microscopy. Islets infused via the bile duct could histologically be found in the parenchymal space. Adequate insulin secretion after glucose stimulation after 1-day and 3-day cultivation verified islet viability and functionality after the repopulation process. We provide the first proof-of-concept for the functionality of islets of Langerhans engrafted in a decellularized rat liver. Furthermore, a re-endothelialization step was implemented to provide implantability. This technique can serve as a bioengineered platform to generate implantable and functional endocrine Neo-Pancreases.
Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare.
(Copyright © 2020. Published by Elsevier Ltd.)
Databáze: MEDLINE
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