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Featured researches published by Maren Ruhnke.


Expert Opinion on Drug Metabolism & Toxicology | 2005

Generation of human hepatocytes by stem cell technology: definition of the hepatocyte.

Jan G. Hengstler; Marc Brulport; Wiebke Schormann; Alexander Bauer; Matthias Hermes; Andreas K Nussler; Fred Fändrich; Maren Ruhnke; Hendrik Ungefroren; Louise Griffin; Ernesto Bockamp; Franz Oesch; Marc-Alexander von Mach

Since 1999, numerous articles have reported the generation of hepatocytes from different types of extrahepatic stem or precursor cells. This opens exciting new possibilities for pharmacology and toxicology, as well as for cell therapy. Hepatocyte marker expression, including albumin, cytokeratin 18, c-met, α-fetoprotein and cytochrome P450 3A4 and -2B6, has been observed after transplantation of different types of human stem cells into the liver of laboratory animals or in vitro after incubation with cytokines. These intriguing observations have prompted scientists to classify stem cell-derived cell populations as hepatocytes. However, this conclusion may be premature. It has been shown that factors of the liver microenvironment can induce expression of a limited number of hepatocyte marker genes in nonhepatic cell types. To conclude on the grounds of a limited number of markers that these cells are true hepatocytes is not indicated. In this case one should carefully evaluate crucial hepatocyte-defining enzymatic properties. The present article: i) reviews studies describing the fate of extrahepatic human stem and precursor cells in livers of laboratory animals, including the possibility of cell fusion; and ii) critically discusses the phenotype of stem cells after application of various differentiation protocols aimed at generating human hepatocytes. In addition, the necessary criteria needed for defining a true hepatocyte are suggested. Establishing the necessary properties for stem cell-derived hepatocytes is timely and reasonable, and thus avoids further misleading semantic confusion. Finally, it is essential to understand that the definition of a bona fide hepatocyte should not be limited to qualitative assays, such as reverse transcriptase polymerase chain reaction and immunohistochemistry, but has to include a quantitative analysis of enzymatic activities, which allows direct comparison with primary hepatocytes. Although the stem cell-derived-hepatocyte does not yet exist there is a good chance that this aim may be achieved in the future.


Transplantation | 2005

Human monocyte-derived neohepatocytes: a promising alternative to primary human hepatocytes for autologous cell therapy.

Maren Ruhnke; Andreas K. Nussler; Hendrik Ungefroren; Jan G. Hengstler; Bernd Kremer; Wolfgang Hoeckh; Thomas Gottwald; P. F. Heeckt; Fred Fändrich

Background. There is growing interest in new therapeutic options for the treatment of end-stage liver diseases. In addition to mechanical devices supporting liver function, such as bioreactors, the transplantation of hepatocyte-like cells derived from (adult) stem cells offer great perspectives. We have generated hepatocyte-like (NeoHep) cells from terminally differentiated peripheral blood monocytes and, in this study, have evaluated these cells as a possible tool for autologous cell therapy. Methods. Peripheral blood monocytes were cultured under conditions that promote hepatocyte-like differentiation and were characterized for hepatocyte marker expression by reverse-transcriptase polymerase chain reaction, immunohistochemistry, and immunoblotting and for specific secretory and metabolic functions with the appropriate biochemical assays. Results. NeoHep cells resembled primary human hepatocytes with respect to morphology, expression of hepatocyte markers (albumin, cytochrome P450 isoenzymes, asialoglycoprotein receptor, coagulation factor VII), various secretory and metabolic functions (albumin secretion, urea production, lactate formation, and lactate dehydrogenase and aspartate transaminase release), and drug detoxification activities (phase I metabolization of ethoxycoumarin into 7OH-coumarin after stimulation with 3-methylcholanthren, induction of CYP3A4 activity, and phase II metabolization through UDP-glucuronidation of 4-methyl-umbelliferone). Conclusions. These data convincingly show that NeoHep cells display a phenotype and specific in vitro metabolic functions that are quantitatively and qualitatively comparable in part with those of primary human hepatocytes. These cells could thus be clinically applied in an autologous setting for the treatment of end-stage liver diseases or for improving liver function in patients who have undergone critical liver-mass resection.


Archive | 2005

Die in vitro Differenzierung von postmitotischen Monozyten in Zelltypen anderer histogenetischer Herkunft beruht auf einer durch M-CSF und IL-3-induzierten partiellen Dedifferenzierung

Hendrik Ungefroren; Maren Ruhnke; Bernd Kremer; Fred Fändrich

Adult stem cells are a good alternative to embryonic stem cells for tissue engineering to be used in organ transplantation and regenerative medicine. Peripheral blood monocytes can be differentiated into highly specialized cell types, e.g. hepatocyte and pancreatic islet-like cells only when cultured initially for a period of 6 days with M-CSF and IL-3. In the presence of M-CSF and IL-3 monocytes resumed proliferation as determined by cell counting, [3H]-thymidine incorporation into nuclear DNA, and activity of the »extracellular signal regulated kinase« (ERK). The newly gained proliferative activity was prevented when cells were exposed to control medium or in cells that were retrovirally transduced with a M-CSF receptor point mutant defective in its ability to transduce a proliferative signal in response to ligand activation. In order to test whether M-CSF+IL-3 induced a dedifferentiation process reverting the normally postmitotic peripheral blood monocyte to a cell with a more uncommitted precursor phenotype, we measured expression of several monopoietic markers and found that ICSBP/IRF-8 and PRDMI, were downregulated, while PU.1 remained constant over the 6-day dedifferentiation period. These results show that a certain degree of in vitro dedifferentiation is required to prime peripheral blood monocytes for subsequent in vitro differentiation into various tissues.


Gastroenterology | 2005

Differentiation of In Vitro–Modified Human Peripheral Blood Monocytes Into Hepatocyte–like and Pancreatic Islet-like Cells

Maren Ruhnke; Hendrik Ungefroren; Andreas K. Nussler; Franz Martín; Marc Brulport; Wiebke Schormann; Jan G. Hengstler; Wolfram Klapper; Karin Ulrichs; James Hutchinson; Bernat Soria; Reza Parwaresch; P. F. Heeckt; Bernd Kremer; Fred Fändrich


Archive | 2003

Dedifferentiated, programmable stem cells of monocytic origin, and their production and use

Bernd Kremer; Fred Fändrich; Maren Ruhnke


Journal of Biological Chemistry | 2005

Transforming Growth Factor-β (TGF-β) Type I Receptor/ALK5-dependent Activation of the GADD45β Gene Mediates the Induction of Biglycan Expression by TGF-β

Hendrik Ungefroren; Stephanie Groth; Maren Ruhnke; Holger Kalthoff; Fred Fändrich


Journal of Orthopaedic Research | 2008

Programmable cells of monocytic origin (PCMO): A source of peripheral blood stem cells that generate collagen type II-producing chondrocytes

Thomas Pufe; Wolf Petersen; Fred Fändrich; Deike Varoga; Christoph Jan Wruck; Rolf Mentlein; Andreas Helfenstein; Daniela Hoseas; Stefanie Dressel; Bernhard Tillmann; Maren Ruhnke


Archive | 2003

Transplant acceptance inducing cells of monocytic origin and their preparation and use

Bernd Kremer; Fred Fändrich; Maren Ruhnke


Langenbeck's Archives of Surgery | 2003

Retroviral endostatin gene transfer inhibits growth of human lung cancer in a murine orthotopic xenotransplant model.

Roland Kurdow; Arnd S. Boehle; Maren Ruhnke; Renata Mendoza; Lars Boenicke; Bence Sipos; Bodo Schniewind; Peter Dohrmann; Holger Kalthoff


Langenbeck's Archives of Surgery | 2004

Tolerance-inducing strategies in transplantation surgery—current status and perspectives

Fred Fändrich; Maren Ruhnke; Bettina Dresske; Bernd Kremer

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Jan G. Hengstler

Technical University of Dortmund

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