| Project/Area Number |
11470262
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Showa University |
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Principal Investigator |
KUSANO Mitsuo Showa University, Dept.of Surgery, School of Medicine Showa University, 教授 (70091569)
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| Co-Investigator(Kenkyū-buntansha) |
ISHII Hiroshi Showa University, Dept.of Surgery, School of Medicine, 講師 (50255725)
MURAKAMI Masahiko Showa University, Dept.of Surgery, School of Medicine, 講師 (70255727)
ITO Yoji Showa University, Dept.of Surgery, School of Medicine, 講師 (10151549)
AOKI Takeshi Showa University, Dept.of Surgery, School of Medicine, 助手 (30317515)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Keywords | hepatocye transplantation / islet cell transplantation / liver regeneration / regenerative medicine / liver support system / pancreatic function support / 肝組織 / 肝血行遮断 / 肝癌 |
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| Research Abstract |
Hepatocyte or pancreatic islets cell transplantations have investigating as an alternative to liver or pancreas transplantation in patients with liver-based metabolic disorders or with severe pancreatitis and diabetes mellitus. Hepatocyte transplantation is making its transition from bench to bedside for acute and chronic liver failure. More than 80 patients have now been transplanted world wide.
A major limiting factor is the availability of good quality cells as human hepatocytes are derived from resected grafts. There is also a need to evaluate the mechanism of liver regeneration that will improve the survival and function of transplanted human hepatocytes. Such approach may allow hepatocyte transplantation to become an accepted and practical alternative to liver transplantation in the near future. To realize this procedure, a hepatocyte bank system capable of supplying large numbers of hepatocytes must be established. We previously reported an easy method for cryopreserving hepatocy
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tes using a microencapsulation technique. Here, we investigated how cryoinjury to microencapsulated hepatocytes could be avoided during cryopreservation. Cryomicroscopy showed that the alginate microencapsulation technique protected the hepatocytes from physical damage caused by the growth of extracellular ice crystals. Ultrastructural examination revealed that the intracellular environment of the microencapsulated hepatocytes was maintained. Our microencapsulation technique protects hepatocytes from cryoinjury. This novel technique could be utilized by hepatocyte banks.
The regulation of liver regeneration after partial hepatectomy (PHx) is complex and involves many different cytokines. We investigated the role of one of these, transforming growth factor-beta1 (TGF-beta1), an inhibitor of liver regeneration. Livers from treated animals contained an increased number of cells in S phase. Antibody administration 24 h after PHx resulted in the highest peak of proliferation ; moreover, peak MIB-5 labeling was also observed at that time. However, neither residual liver-weight-to-body-weight ratios nor regeneration rates differed significantly between any of the animals. These results indicate that TGF-beta1 may inhibit the G1 checkpoint, and serum TGF-beta1 concentration may influence HGF to regulate liver regeneration and to maintain homeostasis of proliferation after PHx. These investigations willl promote hepatocyte or pancreatic cell transplantaion in near future. Less
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