Ong Shin-Yeu, Dai Hui, Leong Kam W
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Tissue Eng. 2006 Dec;12(12):3477-85. doi: 10.1089/ten.2006.12.3477.
The ready availability and low immunogenicity of commercially available mesenchymal stem cells (MSC) render them a potential cell source for the development of therapeutic products. With cell source a major bottleneck in hepatic tissue engineering, we investigated whether commercially available human MSC (hMSC) can transdifferentiate into the hepatic lineage. Based on previous studies that find rapid gain of hepatic genes in bone marrow-derived stem cells cocultured with liver tissue, we used a similar approach to drive hepatic differentiation by coculturing the hMSC with rat livers treated or untreated with gadolinium chloride (GdCl(3)). After a 24-hour coculture period with liver tissue injured by GdCl(3) in a Transwell configuration, approximately 34% of the cells differentiated into albumin-expressing cells. Cocultured cells were subsequently maintained with growth factors to complete the hepatic differentiation. Cocultured cells expressed more hepatic gene markers, and had higher metabolic functions and P450 activity than cells that were only differentiated with growth factors. In conclusion, commercially available hMSC do show hepatic differentiation potential, and a liver microenvironment in culture can provide potent cues to accelerate and deepen the differentiation. The ability to generate hepatocyte-like cells from a commercially available cell source would find interesting applications in liver tissue engineering.
市售间充质干细胞（MSC）易于获取且免疫原性低，使其成为开发治疗产品的潜在细胞来源。鉴于细胞来源是肝组织工程中的一个主要瓶颈，我们研究了市售人MSC（hMSC）是否能转分化为肝系细胞。基于此前的研究发现，与肝组织共培养的骨髓源性干细胞中肝基因迅速增加，我们采用了类似方法，通过将hMSC与经或未经氯化钆（GdCl₃）处理的大鼠肝脏共培养来驱动肝分化。在Transwell装置中与经GdCl₃损伤的肝组织共培养24小时后，约34%的细胞分化为表达白蛋白的细胞。随后用生长因子维持共培养细胞以完成肝分化。与仅用生长因子分化的细胞相比，共培养细胞表达更多肝基因标志物，具有更高的代谢功能和P450活性。总之，市售hMSC确实具有肝分化潜力，培养中的肝脏微环境可提供有力线索来加速和深化分化。从市售细胞来源生成肝细胞样细胞的能力将在肝组织工程中找到有趣的应用。
