Jan Hengstler

Publications (11)41.57 Total impact

• Article: Human hepatocytes: isolation, culture, and quality procedures.

  Daniel Knobeloch, Sabrina Ehnert, Lilianna Schyschka, Peter Büchler, Michael Schoenberg, Jörg Kleeff, Wolfgang E Thasler, Natascha C Nussler, Patricio Godoy, Jan Hengstler, Andreas K Nussler
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  ABSTRACT: The use of isolated human liver cells in research and development has gained increasing interest during the past years. The possible application may vary between elucidation of new biochemical pathways in liver diseases, drug development, safety issues, and new therapeutic strategies up to direct clinical translation for liver support. However, the isolation of human liver cells requires a well-developed logistic network among surgeons, biologists, and technicians to obtain a high quality of cells. Our laboratories have been involved in various applications of human liver cells and we have long-lasting experiences in human liver cell isolation and their application in R&D. We here summarize the present protocol of our laboratories for cell isolation from normal resected liver tissue, the most common tissue available. In addition, we discuss the necessary network in the clinic and quality controls to maintain human liver cells in culture and the effect of 3D extracellular matrix in cultured cells which results in preservation of hepatocyte epithelial polarity in the form of bile canaliculi and repression of epithelial to mesenchymal transitions occurring in 2D cultures.
  Methods in molecular biology (Clifton, N.J.) 01/2012; 806:99-120.
• Article: Susceptibility to urinary bladder cancer: relevance of rs9642880[T], GSTM1 0/0 and occupational exposure.

  Klaus Golka, Matthias Hermes, Silvia Selinski, Meinolf Blaszkewicz, Hermann M Bolt, Gerhard Roth, Holger Dietrich, Hans-Martin Prager, Katja Ickstadt, Jan G Hengstler
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  ABSTRACT: Recently, a genome-wide single nucleotide polymorphism association study has identified a sequence variant 30 kb upstream of the c-Myc gene (allele T of rs9642880) that confers susceptibility to bladder cancer. However, the role of exposure to bladder carcinogens has not been considered. This prompted us to analyse the relevance of this polymorphism in 515 bladder cancer cases and 893 controls where the quality and quantity of occupational exposure to bladder carcinogens has been documented. When we analysed a hospital-based case-control series not selected for occupational exposure, rs9642880[T] was influential, in contrast to GSTM1 0/0. However, in a case-control series of patients that have been occupationally exposed to aromatic amines and polycyclic aromatic hydrocarbons, rs9642880[T] was not influential but GSTM1 0/0 was significantly associated with bladder cancer risk. Therefore, the degree to which rs9642880[T] and GSTM1 0/0 confer susceptibility to urinary bladder cancer seems to depend on the extent of exposure to urinary bladder carcinogens.
  Pharmacogenetics and Genomics 10/2009; 19(11):903-6. · 3.48 Impact Factor
• Article: Predicting drug metabolism-dependent toxicity.

  Hermann M Bolt, Jan G Hengstler
  Archive für Toxikologie 07/2009; 83(7):635-8. · 4.67 Impact Factor
• Article: Alcohol-induced liver injury: how a small molecule overwhelms one of the cell types with the best regeneration capacity of the human body.

  Jan G Hengstler, Patricio Godoy, Joanna D Stewart, Hermann M Bolt
  Archive für Toxikologie 06/2009; 83(6):513-4. · 4.67 Impact Factor
• Article: Mechanisms of telomere maintenance and attrition: linking cancer and ageing.

  Jan G Hengstler, Rosemarie Marchan, Hermann M Bolt
  Archive für Toxikologie 05/2009; 83(5):405-6. · 4.67 Impact Factor
• Article: A rapid and easy to handle thermoluminescence based technique for evaluation of carbon tetrachloride-induced oxidative stress on rat hepatocytes.

  Anika Schumann, Alexander Bauer, Matthias Hermes, Matthias Gilbert, Jan G Hengstler, Christian Wilhelm
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  ABSTRACT: Oxidative stress has become one of the most intensively studied topics in biomedical research and is an often observed mechanism of non-genotoxic carcinogens like carbon tetrachloride. To monitor the oxidative stress status in in vitro hepatocytes, we compared thermoluminescence (TL) measurements with biochemical standard methods for oxidative stress markers. In contrast to biochemical analysis, TL measurements can be performed without any time-consuming extraction procedures by using directly collected cell material. After incubation with CCl(4) (24 h), thermo-induced light emission increased with rising concentration of CCl(4) up to eightfold at 10 mM CCl(4). Simultaneously, we determined the content of different secondary oxidative stress products, like thiobarbituric acid reactive substances and malondialdehyde. The rise of all biochemical markers complied with the increasing concentration of CCl(4). Finally, we could show that the CCl(4)-induced increase of oxidative stress markers determined by time-consuming biochemical methods perfectly correlates with the increase of high temperature bands in rapid TL measurements.
  Archive für Toxikologie 03/2009; 83(7):709-20. · 4.67 Impact Factor
• Article: Low-dose extrapolation in toxicology: an old controversy revisited.

  Hermann M Bolt, Rosemarie Marchan, Jan G Hengstler
  Archive für Toxikologie 03/2009; 83(3):197-8. · 4.67 Impact Factor
• Article: Editorial Manager System for online manuscript submission to Archives of Toxicology.

  Jan Hengstler, Hermann Bolt, Rosemarie Marchan
  Archive für Toxikologie 01/2009; · 4.67 Impact Factor
• Article: Can drinking tea prevent cancer? A controversy revisited.

  Jan G Hengstler, Rosemarie Marchan, Hermann M Bolt
  Archive für Toxikologie 01/2009; 83(1):1-2. · 4.67 Impact Factor
• Article: Tracking of human cells in mice.

  Wiebke Schormann, Friedrich J Hammersen, Marc Brulport, Matthias Hermes, Alexander Bauer, Claudia Rudolph, Markus Schug, Thomas Lehmann, Andreas Nussler, Hendrik Ungefroren, James Hutchinson, Fred Fändrich, Jörg Petersen, Karsten Wursthorn, Martin R Burda, Oliver Brüstle, Kannan Krishnamurthi, Marc von Mach, Jan G Hengstler
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  ABSTRACT: Tracking and tracing of transplanted cells in mice is required in many fields of research. Examples are transplantation of stem cells into organs of mice to study their differentiation capacity and injection of tumor cells to examine metastatic behavior. In the present study we tested the lipid dye CM-DiI and red fluorescent nanoparticles Qdot655 for their applicability in tagging and tracing of human cells in mice. Labeling of different cell types, including MCF-7 human breast cancer cells, human cord blood derived cells, human NeoHep cells and human hepatopancreatic precursor cells, is technically easy and did not compromise further cell culture. After transplantation of CM-DiI or Qdot655 marked cells, red fluorescent structures could be detected already in unprocessed paraffin slices of the studied organs, namely liver, lung, pancreas, kidney, spleen and bone marrow. Next, we examined whether the red fluorescent structures represent the transplanted human cells. For this purpose, we established an in situ hybridization (ISH) technique that allows clear-cut differentiation between human and murine nuclei, based on simultaneous hybridization with human alu and mouse major satellite (mms) probes. We observed a high degree of coincidence between CM-DiI-marked cells and alu positive nuclei. However, also some mms positive cells contained CM-DiI, suggesting phagocytosis of the transplanted CM-DiI-marked cells. The degree of such CM-DiI-positive mouse cells depended on the cell type and route of administration. From a technical point of view it was important that CM-DiI-positive structures in paraffin slices remained fluorescent also after ISH. In contrast, Qdot655 positive structures faded during further staining procedures. In conclusion, marking of cells with CM-DiI or Qdot655 prior to transplantation facilitates recovery of human cells, since a high fraction of positive structures in the host's tissue originate from the transplanted cells. However, CM-DiI or Qdot655 positive staining of individual cells in transplanted tissues is not sufficient to prove their human origin. Additional procedures, such as ISH with alu-probes, are essential, when characterizing individual cells.
  Histochemie 05/2008; 130(2):329-38. · 2.59 Impact Factor
• Article: Regenerative capacity differs between micro- and macrovesicular hepatic steatosis.

  Agnieszka Oleszczuk, Michael Spannbauer, Andrea Tannapfel, Matthias Blüher, Jan Hengstler, Uta-Carolin Pietsch, Annette Schuhmacher, Christian Wittekind, Johann P Hauss, Michael R Schön
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  ABSTRACT: Independent of etiology, the hepatic microvesicular steatosis has a worse prognosis compared with macrovesicular steatosis. Proliferation compensates for apoptosis and reflects regenerative mechanisms following liver injury. It is unknown whether these two types of fatty liver have differences in regenerative capacity and apoptosis, which could have an impact on their prognosis. Two groups of pigs were studied for 72 days under a protein-deficient diet. One group received only protein-deficient diet (n=6), the other was treated in addition to the diet with 6g ethanol/kg/day by means of a percutaneous intragastric catheter (n=6). The rate of proliferating and apoptotic hepatocytes was determined, respectively, by proliferation cell nuclear antigen (PCNA) and ISEL/TUNEL staining for apoptosis in liver biopsies with similar steatosis grade in pigs with micro- or macrovesicular fatty liver. The ethanol-treated group developed microvesicular steatosis, the other group developed macrovesicular steatosis. Proliferation index was significantly increased in macrovesicular in comparison with microvesicular steatosis (p<0.05). Apoptosis rate was similar in both groups. Regeneration, but not apoptosis rate differs between micro- and macrovesicular steatosis. The reduced regenerative capacity in microvesicular steatosis may contribute to the worse prognosis of this subtype of fatty liver disease.
  Experimental and Toxicologic Pathology 11/2007; 59(3-4):205-13. · 2.78 Impact Factor