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Micro‑dimpled surface atelocollagen maintains primary human hepatocytes in culture and may promote their functionality compared with collagen coat culture

  • Authors:
    • Tetsuro Sato
    • Kayoko Semura
    • Ichiro Fujimoto
  • View Affiliations / Copyright

    Affiliations: Koken Research Center, Koken Co., Ltd., Tokyo 115‑0051, Japan
    Copyright: © Sato et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 960-972
    |
    Published online on: June 21, 2019
       https://doi.org/10.3892/ijmm.2019.4251
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Abstract

Primary human hepatocytes (PHHs) are the gold standard for drug development procedures; however, maintaining functional PHHs in vitro is challenging in conventional collagen‑coated cultures. In the present study, we developed a new scaffold comprising high amounts (≥1 mg/cm2) of atelocollagen exposed to ultraviolet radiation to induce cross‑linking and improve stability. Scanning and transmission electron microscopy revealed a micro‑dimpled surface (MDS) scaffold composed of randomly arranged atelocollagen fibrils. The scaffold was therefore designated as MDS atelocollagen. PHHs cultured on MDS atelocollagen were round with a compact cytoplasm and exhibited enhanced levels of albumin (ALB) secretion and cytochrome P450 (CYP) 3A4 activity. The expression of hepatocyte‑related genes, such as serum proteins, drug metabolism‑related CYPs, and nuclear receptors, was enhanced in cells cultured on MDS atelocollagen, but not in those cultured on conventional atelocollagen. Moreover, the abnormal gene expression of cell adhesion molecules observed in conventional atelocollagen culture was suppressed when the cells were grown on MDS atelocollagen, thereby suggesting a cell behavior similar to that of in vivo hepatocytes. These results suggest that MDS atelocollagen functionally preserves PHHs while conserving the simplicity of conventional PHH atelocollagen‑coated cultures.
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Copy and paste a formatted citation
Spandidos Publications style
Sato T, Semura K and Fujimoto I: Micro‑dimpled surface atelocollagen maintains primary human hepatocytes in culture and may promote their functionality compared with collagen coat culture. Int J Mol Med 44: 960-972, 2019.
APA
Sato, T., Semura, K., & Fujimoto, I. (2019). Micro‑dimpled surface atelocollagen maintains primary human hepatocytes in culture and may promote their functionality compared with collagen coat culture. International Journal of Molecular Medicine, 44, 960-972. https://doi.org/10.3892/ijmm.2019.4251
MLA
Sato, T., Semura, K., Fujimoto, I."Micro‑dimpled surface atelocollagen maintains primary human hepatocytes in culture and may promote their functionality compared with collagen coat culture". International Journal of Molecular Medicine 44.3 (2019): 960-972.
Chicago
Sato, T., Semura, K., Fujimoto, I."Micro‑dimpled surface atelocollagen maintains primary human hepatocytes in culture and may promote their functionality compared with collagen coat culture". International Journal of Molecular Medicine 44, no. 3 (2019): 960-972. https://doi.org/10.3892/ijmm.2019.4251
Copy and paste a formatted citation
x
Spandidos Publications style
Sato T, Semura K and Fujimoto I: Micro‑dimpled surface atelocollagen maintains primary human hepatocytes in culture and may promote their functionality compared with collagen coat culture. Int J Mol Med 44: 960-972, 2019.
APA
Sato, T., Semura, K., & Fujimoto, I. (2019). Micro‑dimpled surface atelocollagen maintains primary human hepatocytes in culture and may promote their functionality compared with collagen coat culture. International Journal of Molecular Medicine, 44, 960-972. https://doi.org/10.3892/ijmm.2019.4251
MLA
Sato, T., Semura, K., Fujimoto, I."Micro‑dimpled surface atelocollagen maintains primary human hepatocytes in culture and may promote their functionality compared with collagen coat culture". International Journal of Molecular Medicine 44.3 (2019): 960-972.
Chicago
Sato, T., Semura, K., Fujimoto, I."Micro‑dimpled surface atelocollagen maintains primary human hepatocytes in culture and may promote their functionality compared with collagen coat culture". International Journal of Molecular Medicine 44, no. 3 (2019): 960-972. https://doi.org/10.3892/ijmm.2019.4251
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