Mesenchymal stromal cells: Prevention of post-surgery liver failure after extended partial hepatectomies!

 | Post date: 2021/12/10 | 
Post-surgery liver failure is a serious complication for patients after extended partial hepatectomies (ePHx). mesenchymal stromal cells (MSC) have been reported that improve circulatory maintenance and support multi-organ functions after 70% liver resection. Mechanisms behind the beneficial MSC effects remained unknown. In the latest Nature publication, scientists 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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