中空糸を用いた胚性幹細胞の肝分化誘導プロセス開発とバイオ人工肝臓への応用 Hepatic Differentiation of Embryonic Stem Cells Using Hollow Fibers as a Scaffold and Its Application to a Bioartificial Liver
Embryonic stem cell (ES cell) and induced pluripotent stem cell (iPS cell) have an almost unlimited capacity for self-renewal and potential to differentiate into multiple cell lineages. These cells have much attention as a cell source for a regenerative medicine technology. To realize the therapeutic potential of these stem cells, it is necessary to establish an effective differentiation method from undifferentiated stem cell to specific matured cell. In this study, we investigated the hepatic differentiation of mouse ES cells by the applying hollow fiber (HF)/organoid culture method, in which cultured cells form a cellular aggregate called an "organoid" in the lumen of the HF. ES cells showed high proliferative activity immediately after cell seeding. The expressions of liver-specific functions were detected after about 2 weeks of the hepatic differentiation induction in the HF/organoid culture. As an application of this differentiation technique to regenerative medicine, we designed a hollow fiber-type bioartificial liver device. Because of high proliferative activity of ES cells and high cell density, the maximum expression level of liver-specific functions per unit volume of the device were comparable to that seen in primary mouse hepatocyte culture. In conclusion, the HF/organoid culture method has promise as an effective tool for the differentiation of ES cells into hepatocytes.
膜 37(3), 125-131, 2012-05-01
THE MEMBRANE SOCIETY OF JAPAN