Comparison of human fetal liver, umbilical cord blood, and adult blood hematopoietic stem cell engraftment in NOD-scid/gammac-/-, Balb/c-Rag1-/-gammac-/-, and C.B-17-scid/bg immunodeficient mice.
Comparison of human fetal liver, umbilical cord blood, and adult blood hematopoietic stem cell engraftment in NOD-scid/gammac-/-, Balb/c-Rag1-/-gammac-/-, and C.B-17-scid/bg immunodeficient mice.
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DOI：
10.1016/j.humimm.2009.06.005
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发表时间：
2009-10
期刊：
影响因子：
2.7
通讯作者：
Harding, Martha J.
中科院分区：
文献类型：
--
作者：
Lepus, Christin M.;Gibson, Thomas F.;Gerber, Scott A.;Kawikova, Ivana;Szczepanik, Marian;Hossain, Jaber;Ablamunits, Vitaly;Kirkiles-Smith, Nancy;Herold, Kevan C.;Donis, Ruben O.;Bothwell, Alfred L.;Pober, Jordan S.;Harding, Martha J.
关键词：
携带人类免疫系统成分的免疫缺陷小鼠为研究人类免疫应答提供了一种新方法。我们研究了转移来自孕中期人胎肝（HFL）、脐带血（UCB）或粒细胞集落刺激因子动员的成人血液的CD 34+造血干细胞（HSC）制剂后，发育中的人免疫细胞的数量、表型、发育动力学和功能。（G-CSF-AB）通过肝内注射递送至亚致死剂量辐照的新生NOD-scid/γc−/−、BalB/c-Rag 1 −/−γc−/−和C.B-17-scid/bg小鼠。HFL和UCB HSC提供了最大数量和宽度的发育细胞。NOD-scid/γc−/−和BalB/c-Rag 1 −/−γc−/−在外周血中含有人B和树突状细胞以及人血小板，而NOD-scid/γc−/−小鼠含有更高水平的人T细胞。移植HFL CD 34 + HSC的NOD-scid/γc−/−小鼠表现出人类免疫能力，表现为T依赖性抗原免疫后白色牙髓扩张和总人免疫球蛋白增加，以及抗原激发后迟发型超敏反应浸润白细胞。总之，我们描述了一个令人鼓舞的基础系统，用于研究人类造血谱系的发展和功能，利用人类HFL或UCB HSC移植的NOD-scid/γc−/−小鼠，非常适合未来的研究，以发展一个完全胜任的人源化小鼠模型。
Immunodeficient mice bearing components of a human immune system present a novel approach for studying human immune responses. We investigated the number, phenotype, developmental kinetics and function of developing human immune cells following transfer of CD34+ hematopoietic stem cell (HSC) preparations, originating from second trimester human fetal liver (HFL), umbilical cord blood (UCB), or granulocyte colony-stimulating factor-mobilized adult blood (G-CSF-AB) delivered via intrahepatic injection into sublethally irradiated neonatal NOD-scid/γc−/−, Balb/c-Rag1−/−γc−/−, and C.B-17-scid/bg mice. HFL and UCB HSC provided the greatest number and breadth of developing cells. NOD-scid/γc−/− and Balb/c-Rag1−/−γc−/− harbored human B and dendritic cells as well as human platelets in peripheral blood, whereas NOD-scid/γc−/− mice harbored higher levels of human T cells. NOD-scid/γc−/− mice engrafted with HFL CD34+ HSC demonstrated human immunological competence evidenced by white pulp expansion and increases in total human immunoglobulin following immunization with T-dependent antigens, and delayed type hypersensitivity-infiltrating leukocytes in response to antigenic challenge. In conclusion, we describe an encouraging base system for studying human hematopoietic lineage development and function utilizing human HFL or UCB HSC-engrafted NOD-scid/γc−/− mice that is well suited for future studies toward the development of a fully competent humanized mouse model.
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DOI：
10.3181/0802-rm-70
发表时间：
2008-08
期刊：
Experimental biology and medicine (Maywood, N.J.)
影响因子：
--
作者：
Giassi LJ;Pearson T;Shultz LD;Laning J;Biber K;Kraus M;Woda BA;Schmidt MR;Woodland RT;Rossini AA;Greiner DL
通讯作者：
Greiner DL
影响因子：
32.4
作者：
Li, Wei;Sofi, M. Hanief;Chang, Cheong-Hee
通讯作者：
Chang, Cheong-Hee
影响因子：
2.3
作者：
Mazurier, F;Fontanellas, A;de Verneuil, H
通讯作者：
de Verneuil, H
影响因子：
56.9
作者：
MCCUNE, JM;NAMIKAWA, R;WEISSMAN, IL
通讯作者：
WEISSMAN, IL
影响因子：
6.4
作者：
Akahira-Azuma, M;Szczepanik, M;Askenase, PW
通讯作者：
Askenase, PW