Expanded CD34+ human umbilical cord blood cells generate multiple lymphohematopoietic lineages in NOD-scid IL2rgamma(null) mice.
Expanded CD34+ human umbilical cord blood cells generate multiple lymphohematopoietic lineages in NOD-scid IL2rgamma(null) mice.
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DOI：
10.3181/0802-rm-70
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发表时间：
2008-08
期刊：
影响因子：
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通讯作者：
Greiner DL
中科院分区：
文献类型：
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作者：
Giassi LJ;Pearson T;Shultz LD;Laning J;Biber K;Kraus M;Woda BA;Schmidt MR;Woodland RT;Rossini AA;Greiner DL
脐带血（UCB）越来越多地用于儿童的人类造血干细胞（HSC）移植，但通常需要汇集多个脐带血以获得足够的数量用于成人移植。为了克服这一局限性，我们使用了离体两周培养系统来扩增脐带血中造血CD 34+细胞的数量。为了评估这些扩增的CD 34+细胞的体内功能，将含有1 × 106个CD 34+细胞的培养的人UCB移植到条件NOD-scid IL 2 r γnull小鼠中。扩增的CD 34+细胞显示出短期和长期的再增殖细胞活性。培养的人细胞分化成髓系、B淋巴系和红系，但不分化成T淋巴细胞。在移植前即刻给予受体小鼠人重组TNFα可促进人胸腺细胞和T细胞发育。这些T细胞响应于抗CD 3抗体的TCR交联而剧烈增殖。移植TNFα处理的小鼠产生的抗体响应T依赖性和T非依赖性免疫，当小鼠与B细胞因子BLyS共同处理时，这种免疫增强。离体扩增的CD 34+人UCB细胞在移植到TNFα处理的NOD-scid IL 2 r γnull小鼠后能够产生多种造血谱系和功能性人免疫系统。
Umbilical cord blood (UCB) is increasingly being used for human hematopoietic stem cell (HSC) transplantation in children but often requires pooling multiple cords to obtain sufficient numbers for transplantation in adults. To overcome this limitation, we have used an ex vivo two-week culture system to expand the number of hematopoietic CD34+ cells in cord blood. To assess the in vivo function of these expanded CD34+ cells, cultured human UCB containing 1 × 106 CD34+ cells were transplanted into conditioned NOD-scid IL2rγnull mice. The expanded CD34+ cells displayed short- and long-term repopulating cell activity. The cultured human cells differentiated into myeloid, B-lymphoid, and erythroid lineages, but not T lymphocytes. Administration of human recombinant TNFα to recipient mice immediately prior to transplantation promoted human thymocyte and T-cell development. These T cells proliferated vigorously in response to TCR cross-linking by anti-CD3 antibody. Engrafted TNFα-treated mice generated antibodies in response to T-dependent and T-independent immunization which was enhanced when mice were co-treated with the B cell cytokine BLyS. Ex vivo expanded CD34+ human UCB cells have the capacity to generate multiple hematopoietic lineages and a functional human immune system upon transplantation into TNFα-treated NOD-scid IL2rγnull mice.