We previously found that hepatic progenitor-like cells (HPCs) were enriched in the CD13+CD133+ cell fraction of iPS-differentiated cells. In this study, we focused on the cell surface molecules and analyzed the characteristics of human iPS cell-derived HPCs. Material and Methods: Human iPS cells were differentiated into immature hepatic lineage cells by the addition of cytokines. As well as with anti-CD13 and CD133 antibodies, dissociated

cells were co-stained with a variety of antibodies against cell surface markers (116 types), one antibody at a time, and were analyzed using flow cytometry and in vitro colony formation culture. In addition, cell surface molecules which were positive in CD13+CD133+ HPCs were analyzed the expression during the passage culture. Results: Twenty types of cell surface molecules were Ivacaftor highly expressed in the CD13+CD133+ HPC fraction of iPS-differentiated cells. CD221 (IGF-1 receptor) and CD325 (N-cadherin), part of HPC cell surface markers, were down-regulated during the long-term culture. After the replating step, positive and negative cells of these surface markers were cultured.

Then, CD221+ cells had high proliferative ability compared with CD221- cells. In contrast, the proliferative ability of CD325+ and CD325- cells was ABT-199 mouse not changed. The proliferative ability of HPCs was suppressed by the neutralizing antibody and specific inhibitor of CD221. Overexpression of CD221 in human-iPS cell-derived HPCs increased the number of colony formation of these cells. In MCE公司 addition, IGF-1 and IGF-2 were produced by mouse embryonic fibroblast, which are used as feeder cells in our culture system. Conclusions: This study revealed the expression profile of cell surface molecules in human iPS-derived HPCs and suggested that the IGF receptor signal is important for proliferation of function of hepatic progenitor cells. Disclosures: The following people have nothing to disclose: Kota Tsuruya, Akihide Kamiya, Hiromi Chikada, Kazuya

Anzai, Yoshitaka Arase, Shunji Hirose, Tatehiro Kagawa, Tetsuya Mine Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide. The “stemness” of an HCC, that is, the degree to which it exhibits stem-cell-like properties, is of great interest because this can serve as a prognostic indicator in HCC patients. The stem-like features of cancer cells are conventionally considered to derive from the clonal evolution of relatively differentiated cancer cells through a series of stochastic genetic events; this is known as the clonal evolution model. However, recent functional evidence suggests that the hierarchy of cancer cells is based on the capacity of stem-like cells (cancer stem cells; CSCs) to self-renew and give rise to differentiated cells through asymmetric division, thereby forming heterogeneous populations; this is the CSC model.