|演題||Micro-dimpled surface atelocollagen enhances the function of primary human hepatocytes|
|著者||Tetsuro Sato, Kayoko Semura, Ichiro Fujimoto (KOKEN Research Center, KOKEN Co. Ltd.)|
【背景】Primary human hepatocytes (PHHs) are commonly used as the gold standard for drug development. However, maintaining functional PHHs in vitro has been difficult in conventional collagen coat culture. We developed a new scaffold using atelocollagen.
【方法】The scaffold consists of higher amounts (mg/cm2 order) of atelocollagen, and it was exposed to ultraviolet radiation to induce cross-linking and improve stability.
【結果】Observation using scanning and transmission electron microscopy revealed that the micro-dimpled surface (MDS) scaffold comprised randomly arranged atelocollagen fibrils. Thus, we named this collagen MDS atelocollagen. PHHs cultured on MDS atelocollagen were round with compact cytoplasm, and they exhibited enhanced albumin secretion levels and elevated cytochrome P450 (CYP) 3A4 activity. The expression of hepatocyte-related genes such as serum proteins, drug metabolism-related CYPs and nuclear receptors was maintained in cells cultured on MDS atelocollagen but not in those cultured via conventional collagen culture.
【結論】Therefore, our results suggest that MDS atelocollagen functionally enhances PHHs, conserving the usability of conventional PHHs collagen coat cultures.