Mesenchymal Stem Cells Enhance Liver Regeneration via Improving Lipid Accumulation and Hippo Signaling

间充质干细胞通过改善脂质积累和 Hippo 信号传导增强肝脏再生

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作者:Yang Liu, Faji Yang, Jun Li, Jinglin Wang, Xun Wang, Yuheng Zhang, Xianwen Yuan, Wei Zhu, Xiaolei Shi

Abstract

The liver has the potential to regenerate after injury. It is a challenge to improve liver regeneration (LR) after liver resection in clinical practice. Bone morrow-derived mesenchymal stem cells (MSCs) have shown to have a role in various liver diseases. To explore the effects of MSCs on LR, we established a model of 70% partial hepatectomy (PHx). Results revealed that infusion of MSCs could improve LR through enhancing cell proliferation and cell growth during the first 2 days after PHx, and MSCs could also restore liver synthesis function. Infusion of MSCs also improved liver lipid accumulation partly via mechanistic target of rapamycin (mTOR) signaling and enhanced lipid β-oxidation support energy for LR. Rapamycin-induced inhibition of mTOR decreased liver lipid accumulation at 24 h after PHx, leading to impaired LR. And after infusion of MSCs, a proinflammatory environment formed in the liver, evidenced by increased expression of IL-6 and IL-1β, and thus the STAT3 and Hippo-YAP pathways were activated to improve cell proliferation. Our results demonstrated the function of MSCs on LR after PHx and provided new evidence for stem cell therapy of liver diseases.

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