1999 Fiscal Year Annual Research Report

幹細胞工学を応用した分化型肝細胞の作成とその移植術の開発

Research Project

Project/Area Number	11557091
Research Category	Grant-in-Aid for Scientific Research (B)
Research Institution	Gunma University
Principal Investigator	小暮公孝群馬大学, 医学部, 講師 (80143220)
Co-Investigator(Kenkyū-buntansha)	小島至群馬大学, 生体調節研研究所, 教授 (60143492)
Keywords	肝幹細胞 / 肝細胞培養 / 肝再生 / 肝細胞移植 / アクチビン / フォリスタチン
Research Abstract	本研究では、肝臓から幹細胞を分離し、それを飛躍的に増加させた後に分化させ、その後それを移植するという分化型肝細胞移植法を確立することを目的としている。すなわち少量の肝臓のサンプルから肝の幹細胞を分離培養し、それを増殖させ増量し、次ぎにそれをin vivoで分化させ、高度の分化能を持った細胞にした上で、それを肝切除後の残存肝に自家移植し残存肝の機能を保つという方法の確立をめざしている。本年度は1) ラット肝臓の幹細胞の増殖・分化に関する検討、 2) 分化させた幹細胞の移植方法の検討、 3) 幹細胞の採取と移植の実地、を目標に研究を進めてきた。 1) ではラットから効率のよいviableな肝細胞を採取する条件に関して検討を加え、ほぼ死亡細胞が5%以内という肝細胞ならびに非実質細胞の採取方法を確立することができた。現在、実質細胞を完全に取り除くことにより卵形細胞の増殖スピードが増加することが分かっているので、この系を用いて非実質細胞を完全に取り除き、卵形肝細胞の増殖スピードを増加させる条件を検討している。今後、分子誘導因子アクチビンを作用させることにより、肝細胞への分化を促進する条件決定を行う予定である。 2) では卵形肝細胞にβガラクトシラーゼ遺伝子を導入してマーカーとした後に、卵形肝細胞をin vitroで分化させた上で、肝内に投与し、その後、「分化させた卵形肝細胞」の経過を観察することを目的にしている。現在、予備実験としてlacZ遺伝子を組み込みアデノウイルスベクターを門脈内にone shotで投与し肝細胞内にβ-galactosidaseを過剰に発言させ、肝組織片をX-Galで染色しβ-galactosidaseの活性度を検討していいる。 3) では実際に肝臓を一部採取した後にその組織片から卵形肝細胞を採取しそれを培養系で増加させることを目的にしているがヒトの肝細胞では未だ実施していない。

Research Products

(17 results)

All Other

All Publications (17 results)

[Publications] Kimitaka Kogure: "Role of zctivins and transforming growth factor-b in the regulation of organ mass of the rat liver"Hepatology. (in press). (2000)
[Publications] Kimitaka Kogure: "Relation among portal segmentation,proper hepatic vein and external notch of the caudate lobe in human liver"Annals of Surgery. 231(2). 223-228 (2000)
[Publications] Kimitaka Kogure: "A comparative study of the anatomy of the anatomy of rat and human livers"Journal of Hepatobiliary Pancreatic Surgeries. 6. 171-175 (1999)
[Publications] Kimitaka Kogure: "Evaluation of serum uric acid changes in different forms of hepatic vascular inflow occlusion in human liver surgeries"Life Science. 64(5). 305-313 (1999)
[Publications] Kimitaka Kogure: "Induction of DNA synthesis in intact liver by an administration of follistatin"Abstract(11th World Congress of Gastroenterology). (1998)
[Publications] Kimitaka Kogure: "Immediate onset of DNA synthesis in remnant tat liver after 90% hepatectomy by an administration of follistatin"Journal of Hepatology. 29. 977-984 (1998)
[Publications] Kimitaka Kogure: "Evaluation of serum uric acid changes in different forms of liver surgery"Journal of Hepato-Biliary-Pancreatic Surgery. 4(suppl). 45-45 (1997)
[Publications] Kimitaka Kogure: "Immediate onset of DNA synthesis induced by intraportally administrated follistain in 90% hepatectomized rats"Abstract(37th World Congress of International Society of Surgery). 6. (1997)
[Publications] Kimitaka Kogure: "Uric acid changes in serum during different forms of hepatic vascular inflow occlusion"Life Science. 60(20). 1781-1791 (1997)
[Publications] 小暮公孝: "ペプチド工学を駆使した新たな肝再生法の開発-アクチビン-フォリスタチン系と肝再生-"医科学応用研究財団研究報告. 148-152 (1997)
[Publications] Kimitaka Kogure: "Intrafenous administration of Follistatin;Delivery to the liver and effect of liver rgeneration"Abstract(10th International Congress of Endocrinology). 825-825 (1996)
[Publications] Kimitaka Kogure: "Intrafenous administration of Follistatin;Delivery to the liver and effect of liver rgeneration in 70% hepatectomized rats"Abstract(10th International Congress of Digestive Surgery). 105-105 (1996)
[Publications] Kimitaka Kogure: "The selection of proper therapy for pericholecystic abscess"7th Asian Pacific Congress of Digestive Endoscopy). 404-404 (1996)
[Publications] Kimitaka Kogure: "Effect of Follistatin on liver regeneration after 90 % hepatectomy in the rat"Journal of Hepato-Biliary-Pancreatic Surgery. 3. 367-367 (1996)
[Publications] Kimitaka Kogure: "ntrafenous administration of Follistatin:;Delivery to the liver and effect of liver rgeneration after partial hepatectomy"Hepatology. 242. 361-366 (1996)
[Publications] Kimitaka Kogure: "A single intraportal administration of follistatin accelerates liver regeneration in partially hepatectomized rats"Gastroenterology. 108. 1136-1142 (1995)
[Publications] Kimitaka Kogure: "An administration of follistatin accelerates liver regeneration in partially hepatectomized rats"Abstract:World Congress of Gastroenterology. 315-315 (1994)

1999 Fiscal Year Annual Research Report

幹細胞工学を応用した分化型肝細胞の作成とその移植術の開発

Principal Investigator

小暮 公孝 群馬大学, 医学部, 講師 (80143220)

Research Products

[Publications] Kimitaka Kogure: "Role of zctivins and transforming growth factor-b in the regulation of organ mass of the rat liver"Hepatology. (in press). (2000)

[Publications] Kimitaka Kogure: "Relation among portal segmentation,proper hepatic vein and external notch of the caudate lobe in human liver"Annals of Surgery. 231(2). 223-228 (2000)

[Publications] Kimitaka Kogure: "A comparative study of the anatomy of the anatomy of rat and human livers"Journal of Hepatobiliary Pancreatic Surgeries. 6. 171-175 (1999)

[Publications] Kimitaka Kogure: "Evaluation of serum uric acid changes in different forms of hepatic vascular inflow occlusion in human liver surgeries"Life Science. 64(5). 305-313 (1999)

[Publications] Kimitaka Kogure: "Induction of DNA synthesis in intact liver by an administration of follistatin"Abstract(11th World Congress of Gastroenterology). (1998)

[Publications] Kimitaka Kogure: "Immediate onset of DNA synthesis in remnant tat liver after 90% hepatectomy by an administration of follistatin"Journal of Hepatology. 29. 977-984 (1998)

[Publications] Kimitaka Kogure: "Evaluation of serum uric acid changes in different forms of liver surgery"Journal of Hepato-Biliary-Pancreatic Surgery. 4(suppl). 45-45 (1997)

[Publications] Kimitaka Kogure: "Immediate onset of DNA synthesis induced by intraportally administrated follistain in 90% hepatectomized rats"Abstract(37th World Congress of International Society of Surgery). 6. (1997)

[Publications] Kimitaka Kogure: "Uric acid changes in serum during different forms of hepatic vascular inflow occlusion"Life Science. 60(20). 1781-1791 (1997)

[Publications] 小暮公孝: "ペプチド工学を駆使した新たな肝再生法の開発-アクチビン-フォリスタチン系と肝再生-"医科学応用研究財団研究報告. 148-152 (1997)

[Publications] Kimitaka Kogure: "Intrafenous administration of Follistatin;Delivery to the liver and effect of liver rgeneration"Abstract(10th International Congress of Endocrinology). 825-825 (1996)

[Publications] Kimitaka Kogure: "Intrafenous administration of Follistatin;Delivery to the liver and effect of liver rgeneration in 70% hepatectomized rats"Abstract(10th International Congress of Digestive Surgery). 105-105 (1996)

[Publications] Kimitaka Kogure: "The selection of proper therapy for pericholecystic abscess"7th Asian Pacific Congress of Digestive Endoscopy). 404-404 (1996)

[Publications] Kimitaka Kogure: "Effect of Follistatin on liver regeneration after 90 % hepatectomy in the rat"Journal of Hepato-Biliary-Pancreatic Surgery. 3. 367-367 (1996)

[Publications] Kimitaka Kogure: "ntrafenous administration of Follistatin:;Delivery to the liver and effect of liver rgeneration after partial hepatectomy"Hepatology. 242. 361-366 (1996)

[Publications] Kimitaka Kogure: "A single intraportal administration of follistatin accelerates liver regeneration in partially hepatectomized rats"Gastroenterology. 108. 1136-1142 (1995)

[Publications] Kimitaka Kogure: "An administration of follistatin accelerates liver regeneration in partially hepatectomized rats"Abstract:World Congress of Gastroenterology. 315-315 (1994)

小暮公孝群馬大学, 医学部, 講師 (80143220)