2013 Fiscal Year Final Research Report
Development of the liver lobule-type culture device
| Project/Area Number |
24659591
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
TANIMIZU Naoki 札幌医科大学, 医学部, 講師 (00333386)
SUDO Ryo 慶應義塾大学, 理工学部, 准教授 (20407141)
ICHINOHE Norihisa 札幌医科大学, 医学部, 研究員 (80452978)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | 小型肝細胞 / 胆管上皮細胞 / デバイス / シリコーン / 細胞外基質 / 毛細胆管 / 組織形成 / 内皮細胞 |
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| Research Abstract |
We have developed devices made of silicon for the co-culture of rat small hepatocytes (SHs) and biliary epithelial cells (BECs). Cells could proliferate and survive on a silicon-device that oxygen freely passes through. We coated channels of the silicon-device with various ECM to examine their effects on morphogenesis. However, we have not found an optimal condition for that bile ducts (BDs) reconstructed by BECs connect to bile canaliculi of hepatic organoids reconstructed by matured SHs. By using microfluidic platform, we analyzed angiogenesis in 3D cultures in which collagen gel separated rat mature hepatocytes and endothelial cells (ECs), and found that ECs formed vascular sprouts in collagen gels. Laminins 111 and 521 were necessary for hepatic progenitor cells to differentiate into BECs and to form mature duct structures, respectively. A transcription factor Grhl2 enhanced the morphogenesis of BDs by regulating the expression and the location of claudins 3 and 4.
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