Bioreactor Group, Division of Experimental Surgery:
Dr. med. vet. Katrin Zeilinger
Tel: +49 30
Charité is one of the oldest hospitals in Germany and among the largest of university clinics in Europe today. With a history spanning almost three centuries, Charité has produced eight Nobel Prize winners and has a worldwide reputation for excellence in medicine and research. Currently, with a staff of 10,400 employees, the hospital handles 130,200 inpatient and 497,000 outpatient cases a year.
The Department of General, Visceral, and Transplantation Surgery (Chair: Prof. Dr. P. Neuhaus) belongs to the largest surgical departments in Europe. The special focus of the clinic is on liver surgery, including hepatic resection and liver transplantation. In the department more than 350 hepatectomies and more than 100 liver transplants were performed every year. The department has available 110 in-patient beds and 20 own full intensive care places.
The Workgroup for the Liver of PD Dr. Stockmann specialises in new techniques in liver surgery and transplantation and in liver diagnostics. Extensive research has been carried out in the field of liver regeneration, metabolism, improvement of patient outcome, and health economic analysis. Recently a novel system for the quantitative assessment of liver function (LiMAx test) was developed. This group mainly contributes to WP1. Key persons involved in the d-LIVER project are listed below:
Martin Stockmann, MD, PhD, Consultant and Visceral-Surgeon; Degree MD 1996, PhD 1998, specialized in surgery, visceral surgery, and transplant surgery. Experience in clinical and experimental research of hepatic and gastrointestinal disease (area of interest: liver function, liver regeneration, liver transplantation, liver failure, diagnostics, metabolism, diabetes mellitus, PTDM after LTX, preoperative planning in liver surgery, 3D-CT planning, economic analysis). Lead investigator of multiple single centre clinical trials (IITs) and co-investigator of multiple multi-centre trials.
Tilo Wünsch, PhD, is an international trained postdoc scientist with a strong background in molecular cell biology and metabolism. Before joining Dr. Stockmann’s group he graduated from Jena University, performed his PhD thesis at the Technische Universität München (stipend of the DFG funded graduate school GRK1482) and worked as Postdoc scientist at the Karolinska Institutet Stockholm (Sweden). His scientific focus includes the investigation of pathomechanisms of chronic metabolic and inflammatory diseases, like diabetes or inflammatory bowel disease in a variety of biological in vitro and in vivo test systems. Within the d-LIVER project, Tilo’s work aims to foster translational approaches towards implementation of the d-LIVER homemonitoring techniques into clinical practice. That includes in particular the preparation of required regulatory and ethical documentation, study design, study supervision, data analysis and outcome reporting.
Selected publications in the field of the project
1. Stockmann M, Lock JF, Malinowski M, et al. How to define initial poor graft function after liver transplantation? – a new functional definition by the LiMAx test. Transpl Int 2010:epub.
2. Stockmann M, Lock JF, Malinowski M, Niehues SM, Seehofer D, Neuhaus P. The LiMAx test: a new liver function test for predicting postoperative outcome in liver surgery. HPB 2010;12(2):139-46.
3. Lock JF, Schwabauer E, Martus P, et al. Early Diagnosis of Primary Nonfunction and Indication for Reoperation After Liver Transplantation. Liver Transpl 2010;16(2):172-80.
4. Lock JF, Malinowski M, Schwabauer E, et al. Initial liver graft function is a reliable predictor of tacrolimus trough levels during the first post-transplant week. Clin Transplant 2010:epub.
5. Lock J, Reinhold T, Bloch A, et al. The cost of graft failure and other severe complications after liver transplantation – experience from a German Transplant Center. Ann Transplant 2010;15(3):11-8.
6. Stockmann M, Malinowski M, Lock JF, Seehofer D, Neuhaus P. Factors influencing the indocyanine green (ICG) test: additional impact of acute cholestasis. Hepatogastroenterology 2009;56(91-92):734-8.
7. Stockmann M, Lock JF, Riecke B, et al. Prediction of postoperative outcome after hepatectomy with a new bedside test for maximal liver function capacity. Ann. Surg. 2009;250(1):119-25.
8. Lock JF, Reinhold T, Malinowski M, Pratschke J, Neuhaus P, Stockmann M. The costs of postoperative liver failure and the economic impact of liver function capacity after extended liver resection-a single-center experience. Langenbecks Arch. Surg. 2009;394((6)):1047-56.
The Bioreactor Group, Division of Experimental Surgery is associated to the Berlin Brandenburg Centre for Regenerative Therapies (BCRT) at the Charité, Medical Faculty of the Berlin Universities, Germany. Research at the BCRT focuses on clinical translation of basic science results into therapeutic application in the field of regenerative medicine. Thus, the group is embedded in an environment supporting translational activities to bring laboratory works into clinical use. Within this scope, the group focuses on the development of complex bioreactor technologies for the dynamic 3D perfusion culture of primary cells and stem cells. Research fields of the group concentrate on maintenance and differentiation of liver cells and liver progenitor cells in vitro for clinical extracorporeal liver support; liver cell culture models for laboratory applications in drug development and research; bioreactors for research on adult and embryonic stem cells; skin cell technologies for the treatment of burn injury; production of cells for transplantation in cell-based therapy. Further developments include culture models and technologies for skin-, bone marrow-, and neuronal stem cells. In close university group collaboration, the company StemCellSystems GmbH (P12), provides facilities for bioreactor manufacturing under clean room conditions and according to the requirements of ISO 9001 and ISO 13485 directions. This group mainly contributes to the multi-compartment bioreactor technology used for bio-artificial liver support. Work includes the adaptation and modification of the bioreactor system for sensor integration, in vitro testing of the technology and validation for extracorporeal liver support in patients (WP1, WP3). In addition, the functionality of hepatocytes derived from pancreatic progenitor cells will be investigated in the bioreactor as an alternative to primary liver cells (WP8).
Katrin Zeilinger, Dr. med. vet., head of the Bioreactor Group, has been working at Charité since 1992. She has long-lasting experience in cell culture processing and monitoring, cell characterization and functional cell analyses. Her research works focus on the development of 3D liver cell culture models for in vitro research, culture systems for proliferation and differentiation of adult and embryonic stem cells, and liver cell bioreactor technologies for clinical applications in regenerative medicine.
Marco Richter, Dipl. Ing., Medical Biotech. and Marc Lübberstedt, Dipl. Ing. Biotech., are engaged in 3D liver cell culture, bioengineering of cell systems and bioreactor processing.
Selected publications in the field of the project
- Gerlach JC, Brayfield C, Puhl G, Borneman R, Müller C, Schmelzer E, Zeilinger K. Lidocaine/monoethylglycinexylidide test, galactose elimination test, and sorbitol elimination test for metabolic assessment of liver cell bioreactors. Artif. Organs 2010 Jun;34(6):462-72.
- Lübberstedt M, Müller-Vieira U, Mayer M, Biemel KM, Knöspel F, Knobeloch D, Nüssler AK, Gerlach JC, Zeilinger K. HepaRG human hepatic cell line utility as a surrogate for primary human hepatocytes in drug metabolism assessment in vitro. J. Pharmacol. Toxicol. Methods. 2010 May 8. [Epub ahead of print].
- Schmelzer E, Mutig K, SchradeP, Bachmann S, Gerlach JC, Zeilinger K. Effect of human patient plasma ex vivo treatment on gene expression and progenitor cell activation of primary human liver cells in multi-compartment 3D perfusion bioreactors for extra-corporeal liver support. Biotech. Bioeng. 2009;103(4):817-27.
- Stachelscheid H, UrbaniakT, RingA, SpenglerB, Gerlach JC, Zeilinger K. Isolation and characterization of adult human liver progenitors from ischemic liver tissue. Tissue Eng. Part A. 2008 Dec 24.
- Zeilinger K, HollandG, Sauer IM, Efimova E, KardassisD, ObermayerN, LiuM, Neuhaus P, Gerlach JC. Time course of primary liver cell reorganization in three-dimensional high-density bioreactors for extracorporeal liver support: an immunohistochemical and ultrastructural study. Tissue Eng. 2004, 10(7): 1113-1124.
- Sauer IM, Zeilinger K, Pless G, Kardassis D, Theruvath T, Pascher A, Goetz M, Neuhaus P, Gerlach JC. Extracorporeal liver support based on primary human liver cells and albumin dialysis – treatment of a patient with primary graft non-function. J. Hepatol. 2003; 39 (4): 649 – 653.