Details zur Publikation

Kategorie Textpublikation
Referenztyp Zeitschriften
DOI 10.1038/s41536-021-00194-4
Lizenz creative commons licence
Titel (primär) Mesenchymal stromal cells mitigate liver damage after extended resection in the pig by modulating thrombospondin-1/TGF-β
Autor Nickel, S.; Vlaic, S.; Christ, M.; Schubert, K.; Henschler, R.; Tautenhahn, F.; Burger, C.; Kühne, H.; Erler, S.; Roth, A.; Wild, C.; Brach, J.; Hammad, S.; Gittel, C.; Baunack, M.; Lange, U.; Broschewitz, J.; Stock, P.; Metelmann, I.; Bartels, M.; Pietsch, U.-C.; Krämer, S.; Eichfeld, U.; von Bergen, M.; Dooley, S.; Tautenhahn, H.-M.; Christ, B.
Quelle npj Regenerative Medicine
Erscheinungsjahr 2021
Department MOLSYB
Band/Volume 6
Seite von art. 84
Sprache englisch
Topic T9 Healthy Planet
Abstract Post-surgery liver failure is a serious complication for patients after extended partial hepatectomies (ePHx). Previously, we demonstrated in the pig model that transplantation of mesenchymal stromal cells (MSC) improved circulatory maintenance and supported multi-organ functions after 70% liver resection. Mechanisms behind the beneficial MSC effects remained unknown. Here we performed 70% liver resection in pigs with and without MSC treatment, and animals were monitored for 24 h post surgery. Gene expression profiles were determined in the lung and liver. Bioinformatics analysis predicted organ-independent MSC targets, importantly a role for thrombospondin-1 linked to transforming growth factor-β (TGF-β) and downstream signaling towards providing epithelial plasticity and epithelial-mesenchymal transition (EMT). This prediction was supported histologically and mechanistically, the latter with primary hepatocyte cell cultures. MSC attenuated the surgery-induced increase of tissue damage, of thrombospondin-1 and TGF-β, as well as of epithelial plasticity in both the liver and lung. This suggests that MSC ameliorated surgery-induced hepatocellular stress and EMT, thus supporting epithelial integrity and facilitating regeneration. MSC-derived soluble factor(s) did not directly interfere with intracellular TGF-β signaling, but inhibited thrombospondin-1 secretion from thrombocytes and non-parenchymal liver cells, therewith obviously reducing the availability of active TGF-β.
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Nickel, S., Vlaic, S., Christ, M., Schubert, K., Henschler, R., Tautenhahn, F., Burger, C., Kühne, H., Erler, S., Roth, A., Wild, C., Brach, J., Hammad, S., Gittel, C., Baunack, M., Lange, U., Broschewitz, J., Stock, P., Metelmann, I., Bartels, M., Pietsch, U.-C., Krämer, S., Eichfeld, U., von Bergen, M., Dooley, S., Tautenhahn, H.-M., Christ, B. (2021):
Mesenchymal stromal cells mitigate liver damage after extended resection in the pig by modulating thrombospondin-1/TGF-β
npj Regen. Med. 6 , art. 84 10.1038/s41536-021-00194-4