人肝细胞来源的肝前体样细胞（HepLPCs）通过外泌体传递miRNA调控肝脏再生的作用及其机制研究

慢性肝病常进展至肝硬化，甚至进一步并发肝细胞癌。原位肝移植是治疗单纯重度肝硬化或相伴的肝细胞癌的唯一有效方法，但供体稀缺等因素严重限制了原位肝移植的临床应用。因此，寻找有效方法促进肝再生是肝硬化（包括肝细胞癌）患者长期生存的重要途径和亟待解决的问题。我们前期研究发现基于人肝细胞来源的“肝前体样细胞”具有高度扩增能力，并具有分化为成熟肝细胞和胆管上皮细胞的潜能，可在肝脏组织损伤修复和再生中发挥重要作用，但其作用机制尚未完全明确。本课题拟通过慢性肝硬化模型，重点探讨人肝前体样细胞来源外泌体通过自分泌的miRNA参与肝细胞增殖、促进肝脏组织再生的作用及其具体机制，为临床有效治疗肝硬化以及并发的肝细胞癌等慢性肝损伤提供新的干预靶点和治疗策略。

Chronic liver disease often progresses to cirrhosis, and even to hepatocellular carcinoma (HCC). Orthotopic liver transplantation (OLT) is the only curative therapy to treat simple severe cirrhosis or concomitant HCC. However, the scarcity of donors and other factors seriously limit the clinical application of OLT. Therefore, exploring the effective methods to promote liver regeneration is expected to intervene the patients with liver cirrhosis, including hepatocellular carcinoma. We have previously found that human hepatocyte-derived liver progenitor-like cells(hepLPCs) have a high expansion capacity and can re-differentiate to acquire mature hepatic functions, which play a key role in liver regeneration. However, how hepLPCs promotes liver regeneration in chronic liver disease remains unknown. Based on the models of chronic liver cirrhosis, this study will reveal the role and potential mechanism of hepLPCs-derived exosomal miRNA promotes hepatocyte proliferation and liver tissue regeneration. Thus, Our studies may provide a novel target and therapeutic strategy for the treatment of chronic liver disease.