Improved engraftment of human hematopoietic cells in severe combined immunodeficient (SCID) mice carrying human cytokine transgenes.
Improved engraftment of human hematopoietic cells in severe combined immunodeficient (SCID) mice carrying human cytokine transgenes.
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DOI：
10.1084/jem.182.6.2037
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发表时间：
1995-12-01
影响因子：
15.3
通讯作者：
Bodine, David M.
中科院分区：
文献类型：
--
作者：
Bock, Thomas A.;Orlic, Donald;Dunbar, Cynthia E.;Broxmeyer, Hal E.;Bodine, David M.
我们已经培育出表达人白细胞介素3、粒细胞/巨噬细胞集落刺激因子和干细胞因子基因的免疫缺陷scid-/scid-(SCID)转基因小鼠。我们比较了转基因 SCID 小鼠和两种非转基因 SCID 小鼠中人类造血细胞的植入和分化。将携带 CD34 抗原的人骨髓细胞或人脐带血注射到接受亚致死辐射的受者体内。移植后，通过聚合酶链反应在 28 只转基因 SCID 小鼠中的 14 只的外周血和骨髓中检测到人类 DNA，但在 15 只非转基因 SCID 同窝小鼠中只有 2 只的水平低 10 倍。脐带血移植后8周的骨髓培养物产生人爆发形成单位红细胞、集落形成单位粒细胞/巨噬细胞或粒细胞/红细胞/巨噬细胞/巨核细胞集落。在转基因 SCID 小鼠中观察到植入时间长达 6 个月，是非转基因同窝小鼠或之前每天注射生长因子的移植 SCID 小鼠研究的两倍。我们得出的结论是，人类细胞在 SCID 小鼠中的植入水平和持续时间可以通过人类细胞因子转基因的表达来改善，并且转基因 SCID 小鼠是研究人类造血的有效模型系统。
We have generated immunodeficient scid-/scid- (SCID)-transgenic mice expressing the genes for human interleukin 3, granulocyte/macrophage- colony stimulating factor, and stem cell factor. We have compared engraftment and differentiation of human hematopoietic cells in transgenic SCID mice with two strains of nontransgenic SCID mice. Human bone marrow cells carrying the CD34 antigen or human umbilical cord blood were injected into sublethally irradiated recipients. Human DNA was detected by polymerase chain reaction in peripheral blood and bone marrow of 14 of 28 transgenic SCID mice after transplantation, but in only 2 of 15 nontransgenic SCID littermates at a 10-fold lower level. Bone marrow cultures 8 wk after transplantation of cord blood gave rise to human burst-forming unit erythroid, colony-forming unit granulocyte/macrophage, or granulocyte/erythroid/macrophage/megakaryocyte colonies. Engraftment was observed for up to 6 mo in transgenic SCID mice, twice as long as nontransgenic littermates or previous studies in which transplanted SCID mice were given daily injections of growth factors. We conclude that the level and duration of engraftment of human cells in SCID mice can be improved by expression of human cytokine transgenes and that transgenic SCID mice are an efficient model system for the study of human hematopoiesis.
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影响因子：
56.9
作者：
FLAKE, AW;HARRISON, MR;ZANJANI, ED
通讯作者：
ZANJANI, ED
影响因子：
56.9
作者：
MCCUNE, JM;NAMIKAWA, R;WEISSMAN, IL
通讯作者：
WEISSMAN, IL
影响因子：
20.3
作者：
CHEN, BP;GALY, A;CHEN, SC
通讯作者：
CHEN, SC
影响因子：
56.9
作者：
KIRCHGESSNER, CU;PATIL, CK;BROWN, JM
通讯作者：
BROWN, JM
影响因子：
64.8
作者：
MOSIER, DE;GULIZIA, RJ;WILSON, DB
通讯作者：
WILSON, DB