Basic studies on animal model for regenerative medicine using severe immunodeficient mice.

使用严重免疫缺陷小鼠进行再生医学动物模型的基础研究。

• 批准号: 15300147
• 负责人: ITO Mamoru
• 金额: $ 8.64万
• 依托单位: Central Institute for Experimental Animals
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15300147/
• 关键词: Regenerative medicine; Animal model; NOG mice; ES cells; Rat; Differentiation; 再生医学; 異種移植; 同種移植; 分化

We recently developed severe immunodeficient NOD/Shi-scid, IL-2Rγ KO (NOG) mice by introducing IL-2Rγ^<null> gene into NOD-scid mice. These mice show excellent development and differentiation of human cells, indicating the usefulness of NOG mice to generate "humanized mice". In this study, we investigated the use of NOG mice as models for regenerative medicine. For organ transplantation, human Graff follicles were developed when a small piece of human ovary was transplanted into a renal capsule. The menstrual cycle in the endometrium was also observed when human endometrial tissue was subcutaneously transplanted in the back of the mice followed by injection of human hormones. As a model for regenerative medicine using embryonic stem (ES) cells, we investigated in vivo differentiation of C57BL/6J-derived ES cells after their transplantation in various organs of NOG mice. When ES cells were injected into NOG lungs impaired by treatment with bleomycin or NOG livers impaired by treatment with carbon tetrachloride, ES cells grew and formed teratomas in the organs. However, differentiation of ES cells into lung or liver cells could not be confirmed. We also performed the same experiment using embryonic germ (EG) cells established from SD rats. After rat EG cells were injected into the lung of GFP transgenic SD rats impaired by treatment with bleomycin, the lung was removed and subcutaneously transplanted into the back of NOG mice. At 2, 4 and 8 weeks after transplantation, the implanted lungs were removed and examined histologically. As a result, the implanted lungs were partially engrafted, but the EG cells formed tereratomas. These results suggest that ES cells must be differentiated into progenitor cells but not ES cells by themselves for use in regenerative medicine.

我们最近通过将 IL-2Rγ^<null> 基因导入 NOD-scid 小鼠中，开发了严重免疫缺陷的 NOD/Shi-scid、IL-2Rγ KO (NOG) 小鼠。这些小鼠表现出良好的人类细胞发育和分化能力，表明NOG小鼠可用于产生“人源化小鼠”。在这项研究中，我们研究了使用 NOG 小鼠作为再生医学模型。对于器官移植，当一小块人类卵巢被移植到肾囊中时，就会发育出人类格拉夫卵泡。当将人类子宫内膜组织皮下移植到小鼠背部并注射人类激素时，也观察了子宫内膜的月经周期。作为使用胚胎干 (ES) 细胞的再生医学模型，我们研究了 C57BL/6J 衍生的 ES 细胞移植到 NOG 小鼠的各个器官后的体内分化。当ES细胞被注射到因博来霉素治疗而受损的NOG肺部或因四氯化碳治疗而受损的NOG肝脏中时，ES细胞生长并在器官中形成畸胎瘤。然而，无法证实ES细胞分化为肺细胞或肝细胞。我们还使用 SD 大鼠建立的胚胎生殖 (EG) 细胞进行了相同的实验。将大鼠EG细胞注射到因博莱霉素治疗而受损的GFP转基因SD大鼠的肺部后，取出肺并皮下移植到NOG小鼠的背部。移植后2、4和8周，取出植入的肺并进行组织学检查。结果，植入的肺被部分移植，但EG细胞形成了畸胎瘤。这些结果表明，ES细胞必须分化为祖细胞，而不是ES细胞本身才能用于再生医学。

项目成果

Development of both human connective tissue-type and mucosal-type mast cells in mice from hematopoietic stem cells with identical distribution pattern to human body

• DOI: 10.1182/blood-2003-04-1160
• 发表时间: 2004-02-01
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Kambe, N;Hiramatsu, H;Nakahata, T
• 通讯作者: Nakahata, T

Strain differences in egg collection in rats

大鼠卵收集的菌株差异

• 发表时间: 2004
• 作者: Jiang N;Furue H;Katafuchi T;Yoshimura M;Tomoo Eto
• 通讯作者: Tomoo Eto

Results of karyotype analyses of mouse ES cell lines and germline transmission to the mice

小鼠 ES 细胞系的核型分析结果以及向小鼠的种系传递

• 发表时间: 2004
• 作者: 秋吉一成;澤田晋一;Ayako Sugawara
• 通讯作者: Ayako Sugawara

NOGマウスの特性と再生治療研究への応用

NOG小鼠的特性及其在再生治疗研究中的应用

• 发表时间: 2004
• 作者: 伊藤守

精巣生殖細胞特異的Tact遺伝子の発現制御機構とCpGメチル化

睾丸生殖细胞特异性Tact基因的表达控制机制及CpG甲基化

• 发表时间: 2003
• 作者: S.Yagitani;K.Ishibana;I.Nagano;Y.Nishi;Y.Yoshimura;H.Hayakawa;K.Tsuruda;Masamitsu Haruna;Tatsuhiko SONODA et al.;久野瑞枝
• 通讯作者: 久野瑞枝