Kakinuma Sei, Tanaka Yujiro, Chinzei Ryoko, Watanabe Mamoru, Shimizu-Saito Keiko, Hara Yuzuru, Teramoto Kenichi, Arii Shigeki, Sato Chifumi, Takase Kozo, Yasumizu Takehiko, Teraoka Hirobumi
Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Japan.
Stem Cells. 2003;21(2):217-27. doi: 10.1634/stemcells.21-2-217.
Human umbilical cord blood (UCB) cells have many advantages as grafts for cell transplantation because of the immaturity of newborn cells compared with adult cells. In contrast to their hematopoietic and mesenchymal potential, it remains unclear whether UCB cells have endodermal competence. Here, with a view to utilize UCB cells for cell transplantation into injured liver, we investigated the hepatic potential of UCB cells both in vitro and in vivo. We determined the most efficient conditions leading UCB cells to produce albumin (ALB). In a novel primary culture system supplemented with a combination of growth/differentiation factors, about 50% of UCB cells in 21-day cultures expressed ALB, and the ALB(+) cells coexpressed hepatocyte lineage markers. The ALB-expressing cells were able to proliferate in the culture system. Moreover, in the cell-transplantation model into liver-injured severe combined immunodeficient mice, inoculated UCB cells developed into functional hepatocytes in the liver, which released human ALB into the sera of the recipient mice. In conclusion, this study demonstrates that human UCB is a source of transplantable hepatic progenitor cells. Our findings may have relevance to clinical application of UCB-derived cell transplantation as a novel therapeutic option for liver failure.
与成体细胞相比，新生细胞不成熟，因此人脐带血（UCB）细胞作为细胞移植的移植物具有许多优势。与它们的造血和间充质潜能相反，UCB细胞是否具有内胚层分化能力仍不清楚。为了将UCB细胞用于移植到受损肝脏中，我们在体外和体内研究了UCB细胞的肝潜能。我们确定了使UCB细胞产生白蛋白（ALB）的最有效条件。在一种添加了生长/分化因子组合的新型原代培养系统中，21天培养物中约50%的UCB细胞表达ALB，并且ALB（+）细胞共表达肝细胞谱系标志物。表达ALB的细胞能够在培养系统中增殖。此外，在肝损伤严重联合免疫缺陷小鼠的细胞移植模型中，接种的UCB细胞在肝脏中发育成功能性肝细胞，并将人ALB释放到受体小鼠的血清中。总之，本研究表明人UCB是可移植肝祖细胞的来源。我们的发现可能与UCB来源的细胞移植作为肝衰竭的一种新型治疗选择的临床应用相关。
