Treatment of liver cirrhosis using hepatocyte-derived liver progenitor-like cells: a prospective, open-label, single-arm, safety trial

作者：Kang He, Xuejing Zhu, Yao-Ping Shi, Weijian Huang, Taihua Yang, Zhifeng Xi, Qigen Li, Hanyong Sun, Lijun Qian, Xiaosong Chen, Peiying Li, Xu Zhou, Guiying Gu, Fan Li, Wenming Liu, Cai–Yang Chen, Jie Zhao, Hongping Wu, Fangrong Yan, Michael Ott, Amar Deep Sharma, Hui Liu, Weifeng Yu, Bo Zhai, He‐Xin Yan, Qiang Xia · 发表于：Cell Discovery · 年份：2025 · DOI：10.1038/s41421-025-00831-y · 被引用次数：4 · 研究领域：Liver physiology and pathology、Hepatocellular Carcinoma Treatment and Prognosis、Organ Transplantation Techniques and Outcomes

Liver transplantation remains constrained by the scarcity of donor organs and the risks inherent in the procedure, underscoring the urgent need for novel cirrhosis therapies. We developed a protocol to convert human primary hepatocytes into expandable hepatocyte-derived liver progenitor-like cells (HepLPCs), which secrete high levels of matrix metalloproteinases and hepatocyte growth factor. In a thioacetamide-induced rat model of cirrhosis, human HepLPCs demonstrated potent anti-fibrotic properties and promoted liver regeneration. Biodistribution studies revealed that most xenogenic HepLPCs were cleared from the body within one week, suggesting that their therapeutic benefits likely arise from paracrine signaling rather than long-term engraftment. We initiated a first-in-human clinical trial involving nine patients with cirrhosis to evaluate the feasibility and safety of HepLPCs. Preclinical toxicity assessments in 36 crab-eating macaques confirmed the safety of HepLPC treatment. In the clinical trial, nine patients (mean age: 53 years), primarily with HBV-related cirrhosis, received HepLPCs via trans-hepatic arterial infusion without immunosuppressants. No serious adverse event was observed, and the minor adverse events were consistent with those commonly seen in cirrhosis patients. The treatment was well tolerated, with no transfusion reactions or dose-limiting toxicities. While significant changes in Child-Pugh and MELD scores were not observed, some patients showed impro...