Identification of a novel class of human adherent CD34- stem cells that give rise to SCID-repopulating cells
Identification of a novel class of human adherent CD34- stem cells that give rise to SCID-repopulating cells
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DOI：
10.1182/blood-2002-03-0711
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发表时间：
2003-02-01
期刊：
影响因子：
20.3
通讯作者：
Handgretinger, R
中科院分区：
文献类型：
--
作者：
Kuçi, S;Wessels, JT;Handgretinger, R
在这里，我们描述了一种新型贴壁细胞组分的体外生成，该组分源自高度富集、动员的 CD133(+) 外周血，这些细胞与 Flt3/Flk2 配体和白细胞介素 6 培养 3 至 5 周后。这些细胞缺乏造血干细胞、内皮细胞、间充质细胞、树突状细胞和基质成纤维细胞的标记。然而，所有贴壁细胞均表达粘附分子 VE-钙粘蛋白、CD54 和 CD44。它们的 CD164 和 CD172a（信号调节蛋白-α）以及最近描述的抗体 W7C5 定义的干细胞抗原也呈阳性。贴壁细胞可以自发地或在干细胞因子刺激下产生可移植的、非贴壁的CD133(+)CD34(-)干细胞亚群。这些细胞在体外不产生造血集落。然而，与新鲜分离的CD34(+)细胞相比，将它们移植到非肥胖糖尿病/严重联合免疫缺陷(NOD/SCID)小鼠中可诱导更高的长期多谱系植入，表明这些细胞高度富集SCID重建细胞。除了骨髓谱系细胞外，非贴壁CD34(-)细胞能够产生具有B、T和自然杀伤细胞表型的人类细胞。因此，与CD34(+)干细胞相比，这些细胞具有独特的体内分化潜力，因此可能为移植提供CD34(+)祖细胞的替代选择。 (C) 2003 年，美国血液学会。
Here we describe the in vitro generation of a novel adherent cell fraction derived from highly enriched, mobilized CD133(+) peripheral blood, cells after their culture with Flt3/Flk2 ligand and interleukin-6 for 3 to 5 weeks. These cells lack markers of hematopoietic stem cells, endothelial cells, mesenchymal cells, dendritic cells, and stromal fibroblasts. However, all adherent cells expressed the adhesion molecules VE-cadherin, CD54, and CD44. They were also positive for CD164 and CD172a (signal regulatory protein-alpha) and for a stem cell antigen defined by the recently described antibody W7C5. Adherent cells can either spontaneously or upon stimulation with stem cell factor give rise to a transplantable, nonadherent CD133(+)CD34(-) stem cell subset. These cells do not generate in vitro hematopoietic colonies. However, their transplantation into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice induced substantially higher long-term multilineage engraftment compared with that of freshly isolated CD34(+) cells, suggesting that these cells are highly enriched in SCID-repopulating cells. In addition to cells of the myeloid lineage, nonadherent CD34(-) cells were able to give rise to human cells with B-, T-, and natural killer-cell phenotype. Hence, these cells possess a distinct in vivo differentiation potential compared with that of CD34(+) stem cells and may therefore provide an alternative to CD34(+) progenitor cells for transplantation. (C) 2003 by The American Society of Hematology.