Details
| Original language | English |
|---|---|
| Pages (from-to) | 213-225 |
| Number of pages | 13 |
| Journal | Acta Biomaterialia |
| Volume | 117 |
| Early online date | 16 Sept 2020 |
| Publication status | Published - Nov 2020 |
| Externally published | Yes |
Abstract
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.
Keywords
- Diabetes mellitus, Islets of Langerhans, Neo-Pancreas, Re-endothelialization, Tissue engineering
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biotechnology
- Materials Science(all)
- Biomaterials
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Engineering(all)
- Biomedical Engineering
- Biochemistry, Genetics and Molecular Biology(all)
- Molecular Biology
Sustainable Development Goals
Cite this
- Standard
- Harvard
- Apa
- Vancouver
- BibTeX
- RIS
In: Acta Biomaterialia, Vol. 117, 11.2020, p. 213-225.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Engineering an endothelialized, endocrine Neo-Pancreas
T2 - Evaluation of islet functionality in an ex vivo model
AU - Everwien, Hannah
AU - Keshi, Eriselda
AU - Hillebrandt, Karl H.
AU - Ludwig, Barbara
AU - Weinhart, Marie
AU - Tang, Peter
AU - Beierle, Anika S.
AU - Napierala, Hendrik
AU - Gassner, Joseph MGV
AU - Seiffert, Nicolai
AU - Moosburner, Simon
AU - Geisel, Dominik
AU - Reutzel-Selke, Anja
AU - Strücker, Benjamin
AU - Pratschke, Johann
AU - Haep, Nils
AU - Sauer, Igor M.
N1 - Funding Information: Hannah Everwien was a participant in the BIH-Medical Doctoral Research Stipends program funded by the Charit? ? Universit?tsmedizin Berlin and the Berlin Institute of Health. Dr. K. Hillebrandt is participant in the BIH-Charit? Junior Clinician Scientist Program funded by the Charit?-Universit?tsmedizin Berlin and the Berlin Institute of Health. Priv.-Doz. Dr. B. Struecker was participant in the BIH?Charit? Clinician Scientist Program funded by the Charit? ? Universit?tsmedizin Berlin and the Berlin Institute of Health. Furthermore, we gratefully thank Prof. Dr. S. Bachmann and Mrs. P. Schrade (both Institute of Vegetative Anatomy, Charit? ? Universit?tsmedizin Berlin) for their help. We also thank D. Wyrwal (Department of Surgery, Charit? ? Universit?tsmedizin Berlin) for his help and support during the project. The authors acknowledge the support of the 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. Publisher Copyright: © 2020
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - Diabetes mellitus
KW - Islets of Langerhans
KW - Neo-Pancreas
KW - Re-endothelialization
KW - Tissue engineering
UR - http://www.scopus.com/inward/record.url?scp=85091234388&partnerID=8YFLogxK
U2 - 10.1016/j.actbio.2020.09.022
DO - 10.1016/j.actbio.2020.09.022
M3 - Article
C2 - 32949822
AN - SCOPUS:85091234388
VL - 117
SP - 213
EP - 225
JO - Acta Biomaterialia
JF - Acta Biomaterialia
SN - 1742-7061
ER -