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Basic study towords reconstitution of normal and leukemic human hemopoiesis in small monkey of common marmoset

小狨猴正常和白血病人类造血功能重建的基础研究

基本信息

批准号：
11557073
负责人：
TANI Kenzaburo
金额：
$ 8.64万
依托单位：
The University of Tokyo
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-11557073/
关键词：
common marmoset human hematopoiesis model leukemia model xenograft CD34 positive cell cord blood cells chimera hematopoiesis gene transfer 臍帯血細胞胎児移植 CD34 フローサイトメトリー

项目摘要

For the purpose of constructing preclinical monkey models with normal and leukemic human hematopoiesis, we have introduced small monkey of common marmoset. The followings are the progress in this year.1) Construction of normal and leukemic human hematopoiesis in marmoset :We transplanted CD34 positive human umbilical cord blood cells intraperitoneally to marmoset fetus under the guide of ultrasonograph. We have so far transplanted the CD34 positive human cord blood cells to 16 fetuses in 8 mother marmosets. We have also transplanted human leukemia cells of BV173, IMS-BC1 or Meg-01 to 14 fetuses in 7 mother marmosets. In the beginning abortions followed by the transplantations were experienced but the techniques have been improved using highly sensitive ultrasonography. Now we are following up carefully the in vivo constitution of human/marmoset chimera hematopoiesis in newborn marmosets.2) Characterization of common marmoset lymphocytes : We have isolated marmoset lymphocyte fractions which were positive for human CD4, CD8 or CD56 monoclonal antibodies. The lymphocytes positive for human CD4 or CD8 antibody were considered also to be functional in marmosets. CD56 positive lymphocytes should furthermore be characterized to elucidate its characters.We have so far demonstrated the similar characters of hematopoietic cells and lymphocytes between human and common marmosets. These findings support the possibility of constructing marmoset with human/marmoset hematopoietic chimera. Such marmosets would be very beneficial to study the safety and efficacy of newly developed gene transfer vectors as well as biological modifiers at preclinical levels. Although we have not successfully constructed such chimera marmosets yet, we have developed several new strategies which would make the xenografting more safely and efficiently. Further experiment is required to construct marmoset preclinical model system to study normal and leukemic human hematopoiesis.

为了建立正常人造血和白血病人造血的临床前猴模型，我们引进了普通绒猴。本研究取得了以下进展：1）正常和白血病造血干细胞的建立：在B超引导下，将CD 34阳性人脐血细胞经腹腔移植到绒猴胎儿体内。我们已经将CD 34阳性的人脐血细胞移植到8只母猴的16个胎儿体内。我们还将BV 173、IMS-BC 1或Meg-01的人白血病细胞移植到7只母绒猴的14个胎儿中。起初，进行人工流产和移植手术，但使用高灵敏度的超声波检查技术已得到改进。2）普通绒猴淋巴细胞的鉴定：我们分离了人CD 4、CD 8或CD 56单克隆抗体阳性的绒猴淋巴细胞组分。人CD 4或CD 8抗体阳性的淋巴细胞被认为在绒猴中也有功能。目前，我们已证实人和普通绒猴造血细胞和淋巴细胞的特征相似。这些结果支持了用人/绒猴造血嵌合体构建绒猴的可能性。这些绒猴将非常有益于研究新开发的基因转移载体以及生物修饰剂在临床前水平的安全性和有效性。虽然我们还没有成功地构建这样的嵌合体绒猴，我们已经开发了几种新的策略，这将使异种移植更安全和有效。研究正常人和白血病人的造血功能需要进一步的实验来构建绒猴临床前模型系统。