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Improvement of hepatic function in hepatic cell lines
Germany (BVMD) - Eberhard Karls Universitaet, Tuebingen
Siegfried Weller Institut fuer Unfallmedizinische Forschung Schnarrenbergstrasse 95 72072 Tuebingen
Prof. Dr. rer. nat. Andreas K. Nuessler
Dr. sc. hum. Sabrina Ehnert
Type of Research Project
- Clinical Project with Laboratory work
What is the background of the project?
In vitro toxicity tests are limited by availability of primary human hepatocytes. Therefore, animal testing has been frequently used. However, animal metabolic pathways differ significantly from humans. Therefore, there is a need to develop alternatives: We improve the function of frequently used hepatic cell lines to be similar to primary human hepatocytes. We are currently interested in investigating the role of epigenetic changes in the hepatic cell lines and mesenchymal stem cells. We are also interested in differentiating the mesenchymal stem cells to metabolically active hepatocyte like cells. Aim: Development of alternatives for hepatocyte culture models for testing drug metabolism. The group aims at understanding the factors affecting the differentiation of mesenchymal stem cells to metabolically active and functional hepatocyte like cells. Techniques: Molecuar, biochemical and cell culture techniques; analytical software
What is the aim of the project?
Development of alternatives for hepatocyte culture models for testing drug metabolism. The group aims at understanding the factors affecting the differentiation of mesenchymal stem cells to metabolically active and functional hepatocyte like cells.
What techniques and methods are used?
Molecuar, biochemical and cell culture techniques; analytical software
What is the role of the student?
What are the tasks expected to be accomplished by the student?
participating in the project ( cell culture, isolation of primary hepatocyte, mesenchymal stem cells, RNA isolation, RT-PCR, western blot, toxicity testing, urea analysis, cytochrome assay), profiting from hands-on experience with various techniques, contributing to intercultural exchange, doing experimental evaluations, giving presentations of results, participating in discussion of results, participating in weekly lab meetings
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Basic subject background, weekly trainings and discussions, introduction into techniques
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a presentation - The student will prepare a scientific report
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Basic knowleadge of medical or life science Papers you may consider to read before starting the project: Seeliger C, Culmes M, Schyschka L, Yan X, Damm G, Wang Z, Kleeff J, Thasler WE, Hengstler J, Stoeckle U, Ehnert S, Nuessler AK:Decrease of global methylation improves significantly hepatic differentiation of Ad-MSCs: possible future application for urea detoxification. Cell Transplant. 2013;22(1): 119-131 Ehnert S, Freude T, Eicher C, Burkhardt B, Mart
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Pre-Medical students from the American-British system - Students in biomedical fields
- Seeliger C; Culmes M; Schyschka L; Yan X; Damm G; Wang Z; Kleeff J; Thasler WE; Hengstler J; Stöckle U; Ehnert S; Nüssler AK:Decrease of global methylation improves significantly hepatic differentiation of Ad-MSCs: possible future application for urea detoxification. Cell Transplant. 2013;22(1): 119-131
- Ehnert S; Freude T; Eicher C; Burkhardt B; Martínez Sánchez JJ; Neumann J; Mühl- Benninghaus R; Dooley S; Pscherer S; Nussler AK: Darbepoetin inhibits proliferation of hepatic cancer cells in the presence of TGF-β. Arch Toxicol. 2014;88(1): 89-96
- Godoy P; Schmidt-Heck W; Natarajan K; Lucendo-Villarin B; Szkolnicka D; Asplund A; Björquist P; Widera A; Stöber R; Campos G; Hammad S; Sachinidis A; Chaudhari U; Damm G; Weiss TS; Nüssler A; Synnergren J; Edlund K; Küppers-Munther B; Hay DC; Hengstler JG :Gene networks and transcription factor motifs defining the differentiation of stem cells into hepatocyte-like cells. J Hepatol;63(4): 934-42
- Bitter A; Rümmele P; Klein K; Kandel BA; Rieger JK; Nüssler AK; Zanger UM; Trauner M; Schwab M; Burk O: Pregnane X receptor activation and silencing promote steatosis of human hepatic cells by distinct lipogenic mechanisms. Arch Toxicol;89(11): 2089-103
- Lübberstedt M; Müller-Vieira U; Biemel KM; Darnell M; Hoffmann SA; Knöspel F; Wönne EC; Knobeloch D; Nüssler AK; Gerlach JC; Andersson TB; Zeilinger K: Serum-free culture of primary human hepatocytes in a miniaturized hollow-fibre membrane bioreactor for pharmacological in vitro studies. J Tissue Eng Regen Med;9(9): 1017-26
- Sajadian SO; Ehnert S; Vakilian H; Koutsouraki E; Damm G; Seehofer D; Thasler W; Dooley S; Baharvand H; Sipos B; Nussler AK: Induction of active demethylation and 5hmC formation by 5-azacytidine is TET2 dependent and suggests new treatment strategies against hepatocellular carcinoma. Clin Epigenetics;7(1): 98
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