Lo Iacono Melania, Corrao Simona, Alberti Giusi, Amico Giandomenico, Timoneri Francesca, Russo Eleonora, Cucina Annamaria, Indelicato Sergio, Rappa Francesca, Corsello Tiziana, Saieva Salvatore, Di Stefano Antonino, Di Gaudio Francesca, Conaldi Pier Giulio, La Rocca Giampiero
Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy.
Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90128 Palermo, Italy.
Biology (Basel). 2025 Jan 24;14(2):124. doi: 10.3390/biology14020124.
End-stage liver disease (ESLD), affecting millions worldwide, represents a challenging issue for clinical research and global public health. Liver transplantation is the gold standard therapeutic approach but shows some drawbacks. Hepatocyte transplantation could be a reliable alternative for patient treatment. Mesenchymal stromal cells derived from Wharton's jelly of the umbilical cord (WJ-MSCs) can differentiate into hepatocyte-like cells (HLCs) and show immunomodulatory functions. Due to the increasing demand for fully characterized cell therapy vehicles warranting both the safety and efficacy of treatments, in this work, we extensively characterized WJ-MSCs before and after the application of a hepatocyte-directed differentiation protocol. HLCs exhibited a morphology resembling that of hepatocytes, expressed early and late hepatic markers (α-fetoprotein, albumin, CK18, HNF4-α), and acquired hepatic functions (glycogen synthesis, xenobiotics detoxification), as also revealed by the shotgun proteomics approach. HLCs maintained the same pattern of immunomodulatory molecule expression and mesenchymal markers, other than displaying specific enzymes, suggesting these cells as promising candidates for cellular therapy of ESLD. Our work shed new light on the basic biology of HLCs, suggesting new therapeutic approaches to treat ESLD.
终末期肝病（ESLD）影响着全球数百万人，是临床研究和全球公共卫生面临的一个具有挑战性的问题。肝移植是金标准治疗方法，但存在一些缺点。肝细胞移植可能是患者治疗的可靠替代方法。源自脐带华通氏胶的间充质基质细胞（WJ-MSCs）可分化为肝细胞样细胞（HLCs）并具有免疫调节功能。由于对保证治疗安全性和有效性的完全表征的细胞治疗载体的需求不断增加，在这项工作中，我们在应用肝细胞定向分化方案之前和之后对WJ-MSCs进行了广泛表征。HLCs表现出类似于肝细胞的形态，表达早期和晚期肝脏标志物（甲胎蛋白、白蛋白、细胞角蛋白18、肝细胞核因子4-α），并获得肝脏功能（糖原合成、外源性物质解毒），鸟枪法蛋白质组学方法也揭示了这一点。HLCs除了显示特定酶外，还保持相同的免疫调节分子表达模式和间充质标志物，表明这些细胞是ESLD细胞治疗的有希望的候选者。我们的工作为HLCs的基础生物学提供了新的见解，提出了治疗ESLD的新治疗方法。
