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Development of novel cocktail solutions for cryo-preserving human small hepatocytes and generation of humanoid mouse liver

开发用于冷冻保存人类小肝细胞的新型鸡尾酒溶液并生成人形小鼠肝脏

基本信息

批准号：
18591519
负责人：
MIZUGUCHI Toru
金额：
$ 2.53万
依托单位：
Sapporo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

Hepatocyte transplanation (HT) is an attractive therapeutic modality for liver disease as an alternative for liver organ transplantation. Primary fresh hepatocytes (FHs) are the exclusive cell source that has been used for clinical HT. However, the use of FHs is limited due to a shortage of donor cells. Small hepatocytes (SHs) are hepatic progenitor cells, and can be isolated not only from rodents but also from humans. SHs can proliferate in vitro and express liver functions, although conventional hepatocytes lose them within a short period after culture. SH functions in vivo have never been studied. We therefore investigated HT using SHs to evaluate cell engraftment and function compared to HT using FHs.The donor cell number in the SH group was smaller than that in the FH group at HT. The cell engraftment in the SH group was smaller in the liver and larger in the spleen than in the FH group. The cell engraftment in the liver increased after HT ; however, that in the spleen decreased after HT in both groups. HT using SHs supported the serum albumin level in the NAR experiment as well as that using FH, and albumin mRNA was detectable in the recipients' tissues at 12 weeks after HT.In conclusion, HT using SHs showed hepatic repopulation similar to that using FHs. This suggests that both SHs and FHs can repopulate the liver as if they were hepatic stem cells. In addition, HT using SHs supported liver functions such as albumin correction at the same level as that using FHs. These observations strongly support the idea that SHs could be an alternative to primary FHs as a novel cell source for future HT.

肝细胞移植（HT）作为肝器官移植的替代方案，是一种有吸引力的肝病治疗方式。原代新鲜肝细胞（FHs）是临床治疗HT的唯一细胞来源。然而，由于供体细胞短缺，FHs的使用受到限制。小肝细胞（SHs）是肝祖细胞，不仅可以从啮齿动物中分离出来，也可以从人体内分离出来。尽管常规肝细胞在培养后的短时间内失去了这些功能，但SHs可以在体外增殖并表达肝功能。SH在体内的功能从未被研究过。因此，我们研究了与FHs相比，使用SHs来评估细胞植入和功能的HT。在高温下，SH组供体细胞数量少于FH组。与FH组相比，SH组细胞在肝脏的移植量较小，在脾脏的移植量较大。HT后肝脏细胞植入量增加；然而，两组小鼠脾组织中抗氧化活性均降低。在NAR实验中，使用SHs治疗的小鼠血清白蛋白水平与使用FH治疗的小鼠血清白蛋白水平一致，并且在治疗后12周，受体组织中可检测到白蛋白mRNA。综上所述，使用SHs的肝细胞再生与使用FHs相似。这表明SHs和FHs都可以像肝干细胞一样重新填充肝脏。此外，使用SHs的HT对白蛋白校正等肝功能的支持水平与使用FHs相同。这些观察结果有力地支持了SHs可以替代原代FHs作为未来HT的新细胞来源的观点。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Analysis of the changes pattern of serum apolipoprotein A-1 after hepatectomy.

肝切除术后血清载脂蛋白A-1变化规律分析

DOI：
发表时间：
2006
期刊：
Hepato-Gastrotenterology 53巻2号
影响因子：
0
作者：
Katsuramaki T;Mizuguchi T;Nagayama M;Kimura Y;Furuhata T;Yamauchi K;Hata F;Hirata K.
通讯作者：
Hirata K.

Advantage of post-operative liver function after major hepatectomy using saline-linked cautery

使用盐水连接烧灼对主要肝切除术后肝功能的优势

DOI：
发表时间：
2007
期刊：
影响因子：
0
作者：
Toru;Mizuguchi;Tadashi;Katsuramaki;Minoru;Nagayama;Makoto;Meguro;Takayuki;Nobuoka;Yasutoshi;Kimura;Koji;Yamaguchi;Tomohisa;Furuhata;Koichi;Hirata
通讯作者：
Hirata

Liver repopulation and long-term function of rat small hepatocyte transplantation as an alternative cell source for hepatocyte transplantation.

大鼠小肝细胞移植作为肝细胞移植替代细胞来源的肝脏重建和长期功能。

DOI：
发表时间：
2006
期刊：
Liver Transpl. 12
影响因子：
0
作者：
Shibata C;Mizuguchi T;Kikkawa Y;Nobuoka T;Oshima H;Kawasaki H;Kawamoto M;Katsuramaki T;Mitaka T;Hirata K.
通讯作者：
Hirata K.

A perioperative complication-free coures without a high serum hyaluronate level ensures prolonged disease-free survival and overall survival after hepatectomy for hepatocellular carcinoma

血清透明质酸水平不高的围手术期无并发症可确保肝细胞癌肝切除术后延长无病生存期和总生存期