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.

为了用正常和白血病的人造血构建临床前猴子模型，我们引入了普通果泥的小猴子。以下是今年的进展。1）在摩尔莫斯群岛中构建正常和白血病人类造血症：我们根据超声仪指南将CD34阳性人类脐带血细胞腹膜内移植至摩尔莫斯胎胎儿。到目前为止，我们已经将CD34阳性人脐带血细胞移植到了8个母鸡的16个胎儿。我们还将BV173，IMS-BC1或MEG-01的人类白血病细胞移植到7个母毛果中的胎儿。在开始流产之后，经历了移植，但使用高度敏感的超声检查可以改进这些技术。现在，我们正在仔细跟踪新生儿果果中人类/果泥嵌合体造血的体内构成。2）常见的摩尔莫斯群淋巴细胞的表征：我们具有分离的马莫斯群淋巴细胞级数，这些淋巴细胞部分是人类CD4，CD8或CD56单球蛋白抗体呈阳性的。人CD4或CD8抗体阳性的淋巴细胞也被认为在马莫果中起作用。 CD56阳性淋巴细胞应进一步阐明其特征。到目前为止，我们已经证明了人和普通果果之间的造血细胞和淋巴细胞的相似特征。这些发现支持了用人/摩尔果造血嵌合体构建果胶的可能性。这样的摩尔果会非常有益于研究新开发的基因转移载体的安全性和功效，以及在临床前水平上的生物修饰剂。尽管我们尚未成功构建此类嵌合式果酱，但我们已经制定了几种新策略，这些策略将使Xenografting更加安全有效。需要进一步的实验才能构建摩尔马斯式临床前模型系统，以研究正常和白血病人类造血。