Expansion of human hematopoiteic stem cells in transgenic or large animals.

在转基因动物或大型动物中扩增人类造血干细胞。

• 批准号: 07557077
• 负责人: NAKAUCHI Hiromitsu
• 金额: $ 10.24万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557077/
• 关键词: Hematopoietic stem cells; GM-CSF; IL-3; swine; transgenic mice; SCID mice; Myelodysplastic syndrome; NK cells.; 自己複製; サイトカイン; G-CSF; GM- CSF

1.Engraftment of human hematopoietic cells in transgenic Severe Combined Immunodeficient mice.A transgenic SCID (TG-SCID) mouse expressing the human cytokines interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) has been generated with the aim of making a model system allowing the in vivo proliferation of human hematopoietic cells. Using TG-SCID mice expressing high levels (30-35 ng/ml in the serum) of human GM-CSF and IL-3, we attempted to engraft a human myeloid leukemia cell line, F-36P,derived from a myelodysplastic syndrome (MDS) patient. When F-36P cells were transferred intravenously into sublethally irradiated TG-SCID mice, extensive proliferation of F-36P cells was found four to six weeks later. Successful engraftment, however, required the pre-administration of a monoclonal antibody to mouse interleukin-2 receptor (IL-2R) beta chain, neutralizing NK activity. Surprisingly, all of the transplanted TG-SCID mice engrafted with F-36P cells developed … More hind leg paralysis approximately 6 weeks after transfer. Histological analysis demonstrated extensive invasion and formation of osteolytic lesions by the F-36P cells in the vertebrae. These data indicate that transgenic SCID mice expressing human IL-3 and GM-CSF provide a useful system for the study of human leukemia. In addition, NK cells appear to play an important role in rejection of human cells.2.Transplantation of human hematopoietic cells into miniature-swine and swine fetusTo establish a model for a long-term human hematopoietic reconstitution, human bone marrow or cord blood cells were transplanted into day 45-81 miniature swine or swine fetuses through uterine wall of a pregnant mother. Of the 15 pregnant animals to which transplantation of human hematopoietic cells was performed, five of them gave birth. New born pigs were examined periodically for the presence of human CD45_+ blood cells in peripheral blood and in bone marrow. So far, none of them have human CD45_+ cells above 1% level either in PB or in bone marrow. Less

1.表达thuman cytokines interleukin-3（IL-3）（IL-3）和粒细胞 - 摩噬细胞刺激因子（GM-CSF）的Heman造血室外cemboietic cemboietic cemboietic cemboietic cembotic cembotiot cembinic cembinic cembinic cembinig cembinic cembinic cembinic cembinic cembinic cembinic cembinic cembinic cembinitic ciDeDcICICID（TG-SCID）小鼠的大量Prolity辐照度的TG-SCID小鼠，F-36p细胞的广泛增殖为四到六周后，需要链的预先施用。发育的…在转移后大约6周，椎骨中的F-36p细胞在骨质病变后进行了更多的瘫痪。白血病。猪的胎儿通过15个初级动物的孕妇进行WHMP造血细胞。 +细胞在PB或骨髓中的水平高于1％

项目成果

Masatake Osawa, et al.: "Long-term lymphohematopoietic reconstitution by a single CD34 negative hematopoietic stem cell." J.Immunol.3207-3214 (1996)

Masatake Osawa 等人：“通过单个 CD34 阴性造血干细胞进行长期淋巴造血重建。”

M.Osawa: "Long-term lymphohematopoietic reconstitution by a singli CD34 negative hematopoietic stem cell." Science. Vol.273. 242-245 (1996)

M.Osawa：“单个 CD34 阴性造血干细胞的长期淋巴造血重建。”

Masatake Osawa, et al.: "In vivo self-renewal of c-Kit+ Sca-1+ Linlo/- hematopoietic stem cells." Science.273. 242-245 (1996)

Masatake Osawa 等人：“c-Kit Sca-1 Linlo/- 造血干细胞的体内自我更新。”

Dong, Ku, Kim・et al.: "Engraftment of human myelodysplastic syndrome derived cell line in transgenic severe combined immunodelicient(TG-SCID)mice expressing human GM-CSF and IL-3." Eur.J.Hematol.(in press).

Dong、Ku、Kim 等人：“在表达人 GM-CSF 和 IL-3 的转基因严重联合免疫缺陷 (TG-SCID) 小鼠中植入人骨髓增生异常综合征衍生细胞系。”（出版中） ）。

Shoko Sagara, et al.: "B220 expression by T lymphoid progenitor cells in mouse fetal liver." J.Immunol.158. 666-676 (1997)

Shoko Sagara 等人：“小鼠胎儿肝脏中 T 淋巴祖细胞表达 B220。”