Lim Jung Hwa, Kim Dae Hun, Lee Junhee, Jung Cho-Rok, Kang Hyun Mi
Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
Korea University of Science and Technology (UST), Daejeon, Republic of Korea.
Stem Cells Int. 2025 Apr 23;2025:8953305. doi: 10.1155/sci/8953305. eCollection 2025.
A highly reproducible and functional liver model that closely resembles the human liver plays a crucial role in drug development, disease research, personalized medicine, and regenerative medicine. This study aimed to establish an in vitro liver model using skin epidermal progenitor cells (EPCs), which are easily accessible and exhibit a high proliferative capacity. Skin EPCs with high integrin beta 1 expression demonstrated multipotent differentiation potential, capable of differentiating into adipocyte- and neuron-like cells in vitro. Furthermore, when exposed to high concentrations of activin A, along with Wnt3a and BMP4, these cells efficiently differentiated into definitive endoderm, exhibiting high FOXA2 expression. Under our culture conditions, they further differentiated into functional hepatocytes. These differentiated cells exhibited high albumin secretion, CYP activity, and drug metabolism capabilities similar to those observed in vivo. In conclusion, this study highlights the potential of EPCs to differentiate into functional hepatocytes, providing a feasible and scalable source of hepatocytes for drug screening, liver disease modeling, and potential cell-based therapies.
一种高度可重复且功能完备、与人类肝脏极为相似的肝脏模型在药物研发、疾病研究、个性化医疗及再生医学中发挥着关键作用。本研究旨在利用易于获取且具有高增殖能力的皮肤表皮祖细胞（EPCs）建立一种体外肝脏模型。具有高整合素β1表达的皮肤EPCs表现出多能分化潜能，能够在体外分化为脂肪细胞样和神经元样细胞。此外，当暴露于高浓度的激活素A以及Wnt3a和BMP4时，这些细胞能高效分化为定形内胚层，呈现出高FOXA2表达。在我们的培养条件下，它们进一步分化为功能性肝细胞。这些分化细胞表现出高白蛋白分泌、CYP活性以及与体内观察到的相似的药物代谢能力。总之，本研究突出了EPCs分化为功能性肝细胞的潜力，为药物筛选、肝脏疾病建模及潜在的基于细胞的治疗提供了一种可行且可扩展的肝细胞来源。
