Alliancells Institute of Stem Cells and Translational Regenerative Medicine, Tianjin, China.
Alliancells Institute of Stem Cells and Translational Regenerative Medicine, Tianjin, China; Beijing Alliancells-PuRui Bioscience Co, Ltd, Beijing, China; University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Cytotherapy. 2014 Mar;16(3):309-18. doi: 10.1016/j.jcyt.2013.07.011. Epub 2013 Nov 13.
The protocols for differentiation of hepatocyte-like cells (HLCs) from mesenchymal stromal cells (MSCs) have been well established. Previous data have shown that MSCs and their derived HLCs were able to engraft injured liver and alleviate injuries induced by carbon tetrachloride. The goal of the current study was to determine the differences of MSCs and their derived HLCs in terms of therapeutic functions in liver diseases.
After hepatic differentiation of umbilical cord-derived MSCs in vitro, we detected both MSC and HLC expressions of adhesion molecules and chemokine receptor CXCR4 by flow cytometry; immunosuppressive potential and hepatocyte growth factor expression were determined by means of enzyme-linked immunosorbent assay. We compared the therapeutic effect for fulminant hepatic failure in a mouse model.
MSC-derived-HLCs expressed lower levels of hepatocyte growth factor, accompanied by impaired immunosuppression in comparison with MSCs. Furthermore, undifferentiated MSCs showed rescuing potentials superior to those in HLCs for the treatment of fulminant hepatic failure.
After differentiation, HLCs lost several major properties in comparison with undifferentiated MSCs, which are beneficial for their application in liver diseases. Undifferentiated MSCs may be more appropriate than are HLCs for the treatment of liver diseases.
间充质基质细胞（MSCs）向肝细胞样细胞（HLCs）分化的方案已经成熟。先前的数据表明，MSCs 及其衍生的 HLCs 能够植入受损的肝脏并减轻四氯化碳引起的损伤。本研究的目的是确定 MSCs 和其衍生的 HLCs 在治疗肝脏疾病方面的治疗功能的差异。
在体外将脐带来源的 MSCs 进行肝分化后，我们通过流式细胞术检测黏附分子和趋化因子受体 CXCR4 的 MSC 和 HLC 表达；通过酶联免疫吸附试验测定免疫抑制潜力和肝细胞生长因子的表达。我们比较了在暴发性肝衰竭小鼠模型中的治疗效果。
与 MSCs 相比，MSC 衍生的 HLCs 表达较低水平的肝细胞生长因子，同时伴随免疫抑制作用受损。此外，与 HLC 相比，未分化的 MSCs 对暴发性肝衰竭的治疗具有更好的挽救潜力。
分化后，HLCs 失去了与未分化 MSCs 相比的几个主要特性，这有利于它们在肝脏疾病中的应用。未分化的 MSCs 可能比 HLCs 更适合治疗肝脏疾病。
