Benjamin Strücker, Hendrik Napierala and the rest of the team were awarded with the BIH Paper of the Month for their publication on a new method for developing a transplantable endocrine Neo-Pancreas.

The BIH Paper of the Month is awarded by the BIH Board of Directors to honor a special publication achievement from the joint research space of Charité and MDC. The Paper of the Month is sponsored by the Stiftung Charité as part of its Johanna Quandt Private Excellence Initiative. 

H. Napierala, K.-H. Hillebrandt, N. Haep, P. Tang, M. Tintemann, J. Gassner, M. Noesser, H. Everwien, N. Seiffert, M. Kluge, E. Teegen, D. Polenz, S. Lippert, D. Geisel, A. Reutzel Selke, N. Raschzok, A. Andreou, J. Pratschke, I. M. Sauer & B. Struecker. Engineering an endocrine Neo-Pancreas by repopulation of a decellularized rat pancreas with islets of Langerhans. Scientific Reports 7. Article number: 41777 (2017) doi:10.1038/srep41777

Karl Hillebrandt receives one of the 2017 Einstein Center for Regenerative Therapies (ECRT) Kickbox – Junior Scientist Grant. The project is entitled "Fighting liver cirrhosis? Establishment and analysis of decellularized human cirrhotic liver slices as a 3-dimensional model to study cell matrix interactions".

Liver cirrhosis is one of the main indications for liver transplantation. Due to the organ shortage, this therapy option is limited to the minority of patients suffering from cirrhosis. Therefore, there is a need of alternative treatment options.The aim of our project is to establish a decellularization protocol for human cirrhotic livers slices, which preserves the natural extracellular matrix (ECM) of cirrhotic livers. These decellularized liver slices will serve as a 3 dimensional model to study cell matrix interactions. If we are able to establish a protocol which will preserve the ECM, we will conduct in vitro recellularization experiments to study how the cirrhotic ECM will change the genotype and phenotype of different cell types. With this knowledge we aim to modify specific cell types in vivo or vitro for example prior to cell transplantation. Our ambition is to steer the cell matrix interaction via these modified cells after their transplantation and thereby halt or even reverse the progress of liver cirrhosis. This approach may offer an alternative treatment option in the future.

Team : Karl Hillebrandt, Oliver Klein, Ben Strücker, Igor Sauer  

Scientific Reports accepted our latest paper on „Engineering an endocrine Neo-Pancreas by repopulation of a decellularized rat pancreas with islets of Langerhans“. Authors are H. Napierala, K. Hillebrandt, N. Haep, P. Tang, M. Tintemann, J. Gassner, M. Noesser, H. Everwien, N. Seiffert, M. Kluge, E. Teegen, D. Polenz, S. Lippert, D. Geisel, A. Reutzel-Selke, N. Raschzok, A. Andreou, J. Pratschke, I.M. Sauer, and B. Struecker.
Decellularization of pancreata and repopulation of these non-immunogenic matrices with islets and endothelial cells could provide transplantable, endocrine Neo- Pancreata. In this study, rat pancreata were perfusion decellularized and repopulated with intact islets, comparing three perfusion routes (Artery, Portal Vein, Pancreatic Duct). Decellularization effectively removed all cellular components but conserved the pancreas specific extracellular matrix. Digital subtraction angiography of the matrices showed a conserved integrity of the decellularized vascular system but a contrast emersion into the parenchyma via the decellularized pancreatic duct. Islets infused via the pancreatic duct leaked from the ductular system into the peri-ductular decellularized space despite their magnitude. TUNEL staining and Glucose stimulated insulin secretion revealed that islets were viable and functional after the process.
We present the first available protocol for perfusion decellularization of rat pancreata via three different perfusion routes. Furthermore, we provide first proof-of-concept for the repopulation of the decellularized rat pancreata with functional islets of Langerhans. The presented technique can serve as a bioengineering platform to generate implantable and functional endocrine Neo-Pancreata.

The Journal of Tissue Engineering and Regenerative Medicine accepted our paper „Evolution of graft morphology and function after recellularization of decellularized rat livers“ for publication.

Decellularization of livers is a well-established procedure. Data on different reseeding techniques or the functional evolution and re-organization processes of repopulated grafts remains limited. 

We established a proprietary, customized bioreactor to repopulate decellularized rat livers (n=21) with primary rat hepatocytes (150 x 106 cells) via the hepatic artery and to subsequently evaluate graft morphology and function during seven days of ex vivo perfusion. Grafts were analyzed at 1h, 6h, 12h, 24h, 3d, 5d and 7d after recellularization (all n=3) by immunohistologic evaluation, hepatocyte-related enzyme (AST, ALT, LDH) and albumin measurement in the perfusate. 
To the best of our knowledge, this is the first available protocol for repopulation of rat livers via the hepatic artery. Within the first 24 hours after repopulation, the hepatocytes seemed to migrate out of the vascular network and form clusters in the parenchymal space around the vessels. Graft function increased for the first 24 hours after repopulation with a significantly higher function compared to standard 2D culture after 24 hours. Thereafter, graft function constantly decreased with significantly lower values after six and seven days of perfusion, although histologically viable hepatocytes were found even after this period. Our data suggests that due to a constant loss of function, repopulated grafts should potentially be implanted as soon as cell engraftment and graft re-organization are completed. 

Authors are Antje Butter, Khalid Aliyev, Karl-Herbert Hillebrandt, Nathanael Raschzok, Martin Kluge, Nicolai Seiffert, Peter Tang, Hendrik Napierala, Muhammad Imtiaz Ashraf, Anja Reutzel-Selke, Andreas Andreou, Johann Pratschke, Igor Maximilian Sauer, and Benjamin Struecker.