Ex vivo generation of fully mature human red blood cells from hematopoietic stem cells

Ex vivo generation of fully mature human red blood cells from hematopoietic stem cells
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DOI:
10.1038/nbt1047
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发表时间:
2005-01-01
影响因子:
46.9
通讯作者:
Douay, L
Douay, L
中科院分区:
工程技术1区
文献类型:
--
作者:
Giarratana, MC;Kobari, L;Douay, L

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我们在这里描述了来自多种起源的造血干细胞的成熟人类红细胞(RBC)的大规模生动产生。通过通过在基质细胞上的细胞因子和共培养的应用模仿骨髓微环境,我们将CD34(+)干细胞(高达1.95 x 10(6)倍数的大量扩增与100%末端分化为完全成熟的功能,功能性RBCS(最高1.95 x 10(6)) 。这些细胞与天然RBC一样,在非肥胖/严重的免疫缺陷小鼠中幸存。我们的生产“培养的RBC”的系统将自己用于红细胞生成的基本分析,并提供了一种简单的体外模型,用于研究靶向红细胞细胞的重要人类病毒或寄生虫感染。大规模生产培养的RBC的进一步发展将对基因治疗,输血和热带医学产生影响。
We describe here the large-scale ex vivo production of mature human red blood cells (RBCs) from hematopoietic stem cells of diverse origins. By mimicking the marrow microenvironment through the application of cytokines and coculture on stromal cells, we coupled substantial amplification of CD34(+) stem cells (up to 1.95 x 10(6)-fold) with 100% terminal differentiation into fully mature, functional RBCs. These cells survived in nonobese diabetic/severe combined immunodeficient mice, as do native RBCs. Our system for producing 'cultured RBCs' lends itself to a fundamental analysis of erythropoiesis and provides a simple in vitro model for studying important human viral or parasitic infections that target erythroid cells. Further development of large-scale production of cultured RBCs will have implications for gene therapy, blood transfusion and tropical medicine.