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Title (Primary) Mesenchymal stromal cells mitigate liver damage after extended resection in the pig by modulating thrombospondin-1/TGF-β
Author 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.
Journal npj Regenerative Medicine
Year 2021
Department MOLSYB
Volume 6
Page From art. 84
Language 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.
Persistent UFZ Identifier
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