Die Infektiöse Bursitis ist eine Virusinfektion 3-6 Wochen alter Hühner, die bei Überlebenden mit einer schweren Immunsuppression verbunden ist. Sie verursacht weltweit große wirtschaftliche Schäden. Seit dem Auftreten hoch virulenter (hv) Stämme des Virus der infektiösen Bursits (infectious bursal disease virus, IBDV) Ende der 80-er Jahre blieben viele Fragen zu den biologischen Eigenschaften dieser Virusstämme und einer effektiven Bekämpfung der von ihnen ausgelösten Erkrankung ungeklärt. Unter anderem gelingt es zumeist nicht, hv-Stämme in der Zellkultur zu isolieren. Von besonderem Interesse ist es daher, solche Zellkulturen zu erhalten, die es erlauben, hv-Stämme in vitro zu züchten, ohne dass zuvor deren Genom verändert werden muss. Ziel dieser Arbeit war es daher, geeignete Zellkulturen für die Vermehrung von hv-IBDV-Stämmen zu etablieren und dann einige von deren biologischen Eigenschaften näher zu untersuchen.

Die Infektiöse Bursitis ist eine Virusinfektion 3-6 Wochen alter Hühner, die bei Überlebenden mit einer schweren Immunsuppression verbunden ist. Sie verursacht weltweit große wirtschaftliche Schäden. Seit dem Auftreten hoch virulenter (hv) Stämme des Virus der infektiösen Bursits (infectious bursal disease virus, IBDV) Ende der 80-er Jahre blieben viele Fragen zu den biologischen Eigenschaften dieser Virusstämme und einer effektiven Bekämpfung der von ihnen ausgelösten Erkrankung ungeklärt. Unter anderem gelingt es zumeist nicht, hv-Stämme in der Zellkultur zu isolieren. Von besonderem Interesse ist es daher, solche Zellkulturen zu erhalten, die es erlauben, hv-Stämme in vitro zu züchten, ohne dass zuvor deren Genom verändert werden muss. Ziel dieser Arbeit war es daher, geeignete Zellkulturen für die Vermehrung von hv-IBDV-Stämmen zu etablieren und dann einige von deren biologischen Eigenschaften näher zu untersuchen.

Background: The beneficial impact of mesenchymal stem cells (MSC) on both acute and chronic liver diseases has been confirmed, although the molecular mechanisms behind it remain elusive. We aim to identify factors secreted by undifferentiated and hepatocytic differentiated MSC in vitro in order to delineate liver repair pathways potentially targeted by MSC. Methods: Secreted factors were determined by protein arrays and related pathways identified by biomathematical analyses. Results: MSC from adipose tissue and bone marrow expressed a similar pattern of surface markers. After hepatocytic differentiation, CD54 (intercellular adhesion molecule 1, ICAM-1) increased and CD166 (activated leukocyte cell adhesion molecule, ALCAM) decreased. MSC secreted different factors before and after differentiation. These comprised cytokines involved in innate immunity and growth factors regulating liver regeneration. Pathway analysis revealed cytokine-cytokine receptor interactions, chemokine signalling pathways, the complement and coagulation cascades as well as the Januskinase-signal transducers and activators of transcription (JAK-STAT) and nucleotide-binding oligomerization domain-like receptor (NOD-like receptor) signalling pathways as relevant networks. Relationships to transforming growth factor beta(TGF-beta) and hypoxia-inducible factor 1-alpha (HIF1-alpha) signalling seemed also relevant. Conclusion: MSC secreted proteins, which differed depending on cell source and degree of differentiation. The factors might address inflammatory and growth factor pathways as well as chemo-attraction and innate immunity. Since these are prone to dysregulation in most liver diseases, MSC release hepatotropic factors, potentially supporting liver regeneration.

Background: The beneficial impact of mesenchymal stem cells (MSC) on both acute and chronic liver diseases has been confirmed, although the molecular mechanisms behind it remain elusive. We aim to identify factors secreted by undifferentiated and hepatocytic differentiated MSC in vitro in order to delineate liver repair pathways potentially targeted by MSC. Methods: Secreted factors were determined by protein arrays and related pathways identified by biomathematical analyses. Results: MSC from adipose tissue and bone marrow expressed a similar pattern of surface markers. After hepatocytic differentiation, CD54 (intercellular adhesion molecule 1, ICAM-1) increased and CD166 (activated leukocyte cell adhesion molecule, ALCAM) decreased. MSC secreted different factors before and after differentiation. These comprised cytokines involved in innate immunity and growth factors regulating liver regeneration. Pathway analysis revealed cytokine-cytokine receptor interactions, chemokine signalling pathways, the complement and coagulation cascades as well as the Januskinase-signal transducers and activators of transcription (JAK-STAT) and nucleotide-binding oligomerization domain-like receptor (NOD-like receptor) signalling pathways as relevant networks. Relationships to transforming growth factor beta(TGF-beta) and hypoxia-inducible factor 1-alpha (HIF1-alpha) signalling seemed also relevant. Conclusion: MSC secreted proteins, which differed depending on cell source and degree of differentiation. The factors might address inflammatory and growth factor pathways as well as chemo-attraction and innate immunity. Since these are prone to dysregulation in most liver diseases, MSC release hepatotropic factors, potentially supporting liver regeneration.