Developing a 3D-printed artificial liver derived from canine induced pluripotent or somatic stem cells
Project/Area Number |
17K08116
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Veterinary medical science
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Research Institution | Azabu University |
Principal Investigator |
Neo Sakurako 麻布大学, 獣医学部, 講師 (50532107)
|
Project Period (FY) |
2017-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
Keywords | 細胞凝集塊 / 肝細胞 / 犬 / 3Dプリンター / 人工肝組織 / 再生医療 / 再生医学 |
Outline of Final Research Achievements |
One disadvantage of the conventional human hepatocyte monolayer culture method is that resulting cells exhibit a shorter lifespan and are unable to stably maintain liver-specific functions, including cytochrome P450 (CYP450) activity. This study thus aimed to develop an ex vivo artificial liver exhibiting sustained CYP450 activity. Canine primary cultured hepatocyte (cHep) or bone marrow stem cell (cBMSC)-derived hepatocyte-like cells (ciHep) were co-cultured with human umbilical vein endothelial cells (HUVECs) and adipose tissue-derived mesenchymal stem cells (AD-MSCs) to generate φ500μm spheroids. Relative to spheroids containing ciHep, those containing cHep maintained a higher day-three level of CYP450 gene expression. Spheroids were inserted into the “Kenzan” using a 3D bio-printer (Rejenova®) and cultured in a perfusion chamber for seven days to prepare artficial liver structures. Histologically, hepatocytes were MSC-coated.
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Academic Significance and Societal Importance of the Research Achievements |
本研究で得られた細胞凝集塊作製条件を用いて犬人工肝組織を作製することに成功すれば、創薬の毒性試験に応用が期待でき、動物実験代替法ともなる。「動物実験数の大幅削減」を求める現代社会の動きに対応するだけでなく、「信頼性の高い薬物動態や毒性試験の結果が求められる」という難題に直面している医学・創薬および獣医学研究における有力な解決策の一つになる。
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Report
(4 results)
Research Products
(3 results)