Human Liver Cell and Pancreatic Cell Transplantation-Study Using Resected Liver and Pancreas Segment-

人类肝细胞和胰腺细胞移植-使用切除的肝脏和胰腺段进行研究-

• 批准号: 11470262
• 负责人: KUSANO Mitsuo
• 金额: $ 3.07万
• 依托单位: Showa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470262/
• 关键词: 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

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 … More 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

肝细胞或胰岛细胞移植已被研究作为肝脏或胰腺移植的替代方案用于肝脏代谢紊乱或严重胰腺炎和糖尿病患者。肝细胞移植治疗急性和慢性肝功能衰竭正从实验室向临床过渡。目前，全世界已有80多名患者接受了移植手术。一个主要的限制因素是高质量细胞的可获得性，因为人类肝细胞来源于切除的移植物。还需要评估肝脏再生的机制，以提高移植的人肝细胞的存活率和功能。这种方法可能使肝细胞移植在不久的将来成为肝移植的一种可接受和实用的替代方法。为了实现这一过程，必须建立一个能够供应大量肝细胞的肝细胞库系统。我们之前报道了一种简单的冷冻保存肝细胞的方法，更多的是使用微胶囊技术。在这里，我们研究了在冷冻保存过程中如何避免对微囊化肝细胞的冷冻损伤。低温显微镜观察表明，海藻酸盐微胶囊技术可保护肝细胞免受细胞外冰晶生长造成的物理损伤。超微结构检查显示微囊化肝细胞的胞内环境得到维持。我们的微胶囊技术可以保护肝细胞免受低温损伤。这项新技术可用于肝细胞库。部分肝切除术后肝脏再生的调控是复杂的，涉及许多不同的细胞因子。我们研究了其中之一的作用，转化生长因子- β 1 (tgf - β 1)，一种肝脏再生抑制剂。经处理的动物肝脏中S期细胞数量增加。PHx后24 h给药，细胞增殖达到高峰；同时也观察到峰值的MIB-5标记。然而，在任何动物之间，剩余肝脏重量与体重的比率和再生率都没有显着差异。这些结果表明，TGF-beta1可能抑制G1检查点，血清TGF-beta1浓度可能影响HGF调节PHx后肝脏再生和维持增殖稳态。这些研究将在不久的将来促进肝细胞或胰腺细胞的移植。少

项目成果

【肝疾患診療マニュアル】肝疾患の診断と治療の進め方 その他の腫瘍性病変肝癌類似病変

【肝病治疗手册】肝病诊断与治疗 其他肿瘤性病变 肝癌样病变

• 发表时间: 1999
• 期刊: 日本医師会雑誌 122巻8号
• 作者: 草野満夫

再生肝の再々生能に関する検討 再肝切除モデルによる

基于再肝切除模型的再生肝再生能力研究

• 发表时间: 1999
• 期刊: 日本消化器外科学会雑誌 32巻2号
• 作者: 青木武士;村上雅彦;草野満夫
• 通讯作者: 草野満夫

A novel method of cryopreservation of rat and human hepatocytes by using encapsulation technique and possible use for cell transplantation

• DOI: 10.3727/000000005783982710
• 发表时间: 2005-01-01
• 期刊: CELL TRANSPLANTATION
• 影响因子: 3.3
• 作者: Aoki, T;Koizumi, T;Kusano, M
• 通讯作者: Kusano, M

Cold preservation of the liver with oxygenation by a two-layer method

两层法充氧肝脏冷藏

• 发表时间: 2009
• 期刊: J Surg Res. 152(2)
• 作者: Odaira M;Aoki T;Miyamoto Y;Yasuhara R;Jin Z;Yu J;Nishino N;Yamada K;Kusano T;Hayashi K;Yasuda D;Koizumi T;Mitamura K;Enami Y;Niiya T;Murai N;Kato H;Shimizu Y;Kamijyo R;Kusano M.
• 通讯作者: Kusano M.

Long-term maintenance of the drug transport activity in cryopreservation of microencapsulated rat hepatocytes

微囊化大鼠肝细胞冻存中药物转运活性的长期维持

• 发表时间: 2007
• 期刊: Cell Transplant 16(1)
• 作者: Koizumi T;Aoki T;Kobayashi Y;Yasuda D;Izumida Y;Jin Z;Nishino N;Shimizu Y;Kato H;Murai N;Niiya T;Enami Y;Mitamura K;Yamamoto T;Kusano M.
• 通讯作者: Kusano M.