| Project/Area Number |
11308036
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biological material science
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| Research Institution | Keio University |
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Principal Investigator |
ISHII Hiromasa Keio University School of Medicine, Internal Medicine, Professor, 医学部, 教授 (20051500)
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| Co-Investigator(Kenkyū-buntansha) |
AZUMA Toshifumi Keio University School of Medicine, Internal Medicine, Instructor, 医学部, 助手 (00222612)
SUEMATSU Makoko Keio University School of Medicine, Biochemistry and Integrative Medical Biology, Professor, 医学部, 教授 (00206385)
SUZUKI Hidekazu Keio University School of Medicine, Internal Medicine, Instructor, 医学部, 助手 (70255454)
赤池 敏宏 東京工業大学, 生命理工学部, 教授 (30101207)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥35,400,000 (Direct Cost: ¥34,800,000、Indirect Cost: ¥600,000)
Fiscal Year 2001: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2000: ¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 1999: ¥26,900,000 (Direct Cost: ¥26,900,000)
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| Keywords | Artificial Liver Support / Mixed culture / Matrix / Stem cell / Apoptosis / Hepatocyte / Ito cell / Microfabrication / マイクロファブレケーション / アルブミン / ステムセル |
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| Research Abstract |
Cell- cell interactions are important in embryogenesis, in adult physiology and pathophysiology of many disease processes. Co-cultivation of parenchymal and mesenchymal cells has been widely utilized as a paradigm for the study of cell-cell interactions in vitro. In addition, co-cultures of two cell types provide highly functional tissue constructs for use in therapeutic or investigational applications. In this study, we utilize micro fabrication techniques to localize both cell populations in patterned configulations on rigid substrates. We were able to control the level of homotypic interaction in cultures of single cell type and the degree of heterotypic contact in co-culture over a wide range. We have experimentally shown that stellate cells numbers and increased heterotipic cell-cell interactions influences hepatocellular functions. Organs are composed of many individual cell types and together responsible for orchestrating tissue functions. We could mimic liver function in vitro
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and utilize this sytem to elucidate fundamental factors of liver development. We monitored liver -specific functions by urea synthesis and albumin secretion, varied 2-fold with increasing heterotipic cell-cell interactions. Urea is a marker of metabolic function and albumin secretion is a marker of synthetic function. We also investigated lipid metabolism and P450 enzymatic detoxification activity. All data indicated that increasing heterotipic cell-cell interactions contributed maintaining liver specific functions. Moreover we could induced some hepatocyte specific protein expression in ES cells when we co-cultivate ES cells in this system. These evidence indicate that this approach will allow further elucidation of the complex interplay betweentwo cell types as they form a functional model tissue in vitro or as they interact in vivo to form functional organ. Although further investigations are necessary to develop artificial liver for clinical use, this study has clearly shown that appropriate co-clutivation method is numers of advantage over the other approaches. Less
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