Reconstruction of the liver useing autologous bone marrow

使用自体骨髓重建肝脏

• 批准号: 16209038
• 负责人: TAKAYAMA Tadatoshi
• 金额: $ 28.79万
• 依托单位: Nihon University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16209038/
• 关键词: liver regeneration; bone marrow stem cell; Transdifferentiation; chemokine; gene chip

Background/Aims: Bone marrow cells are highly plastic and differentiate into various cell types, including hepatocytes. To explore the mechanisms underlying these processes, we focused on the initial responses of bone marrow to hepatectomy, using a mouse model.Methods: To evaluate hepatic differentiation in bone marrow cells we measured hepatocyte-related gene expression in mice undergoing partial hepatectomy with or without pretreatment for 1 week with 2-acetyl aminofluorene (AAF).Results: Hepatectomy induced several genes related to early hepatic differentiation in bone marrow. Expression of these genes was enhanced by the administration of AAF, whereas genes specific for mature hepatocytes were not detected. We characterised the bone marrow cell population expressing hepatocyte differentiation genes. a-fetoprotein mRNA was induced in Lin-and either CD34+, c-kit+, Sca-1+, CD49f+ or CD45+ cells. The genes upregulated in the liver after AAF treatment and hepatectomy were identified using oligonucleotide microarrays. These included genes associated with the acute phase response. Dexamethasone inhibited the expression of early hepatic differentiation genes in the bone marrow of AAF/PHx mice.Conclusions: Early hepatic differentiation genes were induced in bone marrow in response to hepatectomy, especially when regeneration of the remnant liver was suppressed. Circulating signals generated in the AAF/PHx liver might activate this differentiation.

背景/目的：骨髓细胞具有高度可塑性，可分化为多种细胞类型，包括肝细胞。为了探索这些过程背后的机制，我们使用小鼠模型研究了骨髓对肝切除术的初始反应。方法：为了评估骨髓细胞的肝分化，我们对部分肝切除小鼠进行了2-乙酰氨基芴（AAF）预处理或不预处理1周，测量了肝细胞相关基因的表达。结果：肝切除术诱导了几个与骨髓早期肝分化相关的基因。这些基因的表达通过AAF得到增强，而成熟肝细胞特异性基因未被检测到。我们对表达肝细胞分化基因的骨髓细胞群进行了表征。在lin和CD34+、c-kit+、Sca-1+、CD49f+或CD45+细胞中诱导a-胎蛋白mRNA。使用寡核苷酸微阵列技术鉴定AAF治疗和肝切除术后肝脏中上调的基因。其中包括与急性期反应相关的基因。地塞米松抑制AAF/PHx小鼠骨髓中早期肝分化基因的表达。结论：早期肝分化基因在肝切除术后的骨髓中被诱导，特别是当残肝再生受到抑制时。在AAF/PHx肝脏中产生的循环信号可能激活了这种分化。

项目成果

Efficacy of engineered liver tissue based on poly-L-lactic acid scaffolds and fetal mouse liver cells cultured with oncostatin M, nicotinamide, and dimethyl sulfoxide.

• DOI: 10.1089/ten.2004.10.1577
• 发表时间: 2004-11
• 期刊: Tissue engineering
• 作者: Jinlan Jiang;N. Kojima;Lei Guo;K. Naruse;M. Makuuchi;A. Miyajima;Weiqun Yan;Y. Sakai

Endoscopic management of biliary complications after adult living donor liver transplantation

• DOI: 10.1111/j.1572-0241.2004.30775.x
• 发表时间: 2004-07-01
• 期刊: AMERICAN JOURNAL OF GASTROENTEROLOGY
• 影响因子: 9.8
• 作者: Shah, JN;Ahmad, NA;Ginsberg, GG
• 通讯作者: Ginsberg, GG

Systematic grading of surgical complications in live liver donors according to Clavien's system

根据 Clavien 系统对活体肝脏捐献者的手术并发症进行系统分级

• 发表时间: 2006
• 期刊: Transpl Int 19(12)
• 作者: Sumihito Tamura;Yasuhiko Sugawara;Junichi Kaneko;Noriyo Yamashiki;Yoji Kishi;Yuichi Matsui;Norihriro Kokudo;Masatoshi Makuuchi
• 通讯作者: Masatoshi Makuuchi

Impact of incidentally found hepatocellular carcinoma on the outcome of living donor liver transplantation

偶然发现的肝细胞癌对活体肝移植结局的影响

• 发表时间: 2006
• 期刊: Transplant International 19(9)
• 作者: Kiyoshi Hasegawa;Tadatoshi Takayama;Masayoshi Ijichi;Yutaka Matsuyama;Hiroshi Imamura;Keiji Sano;YasuhikoSugawara;Norihriro Kokudo;Masatoshi Makuuchi;Kishi Y. Sugawara Y. Tamura S. Kaneko J. Kokudo N. Makuuchi M
• 通讯作者: Kishi Y. Sugawara Y. Tamura S. Kaneko J. Kokudo N. Makuuchi M

Methylation status of suppressor of cytokine signaling-1 gene in hepatocellular carcinoma

• DOI: 10.1007/s00535-003-1343-0
• 发表时间: 2004-06-01
• 期刊: JOURNAL OF GASTROENTEROLOGY
• 影响因子: 6.3
• 作者: Miyoshi, H;Fujie, H;Koike, K
• 通讯作者: Koike, K