Novel method for efficient production of multipotential hematopoietic progenitors from human embryonic stem cells

Novel method for efficient production of multipotential hematopoietic progenitors from human embryonic stem cells
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DOI:
10.1532/ijh97.06203
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发表时间:
2007-06-01
影响因子:
2.1
通讯作者:
Tsuji, Kohichiro
Tsuji, Kohichiro
中科院分区:
医学4区
文献类型:
--
作者:
Ma, Feng;Wang, Dan;Tsuji, Kohichiro

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我们提出了一种新的方法,通过与小鼠胎肝来源的基质细胞共培养,从人胚胎干细胞(hESC)的造血祖细胞的有效生产,其中胚胎造血显着扩大在妊娠中期。我们在共培养中产生了各种造血祖细胞,并且这种造血活性集中在来自分化的hESC的鹅卵石样细胞中。鹅卵石样细胞主要表达CD 34,并保留了内皮细胞的潜力。它们还含有造血集落形成细胞,特别是红系和多系集落形成细胞的高频率。鹅卵石样细胞中丰富的多能造血祖细胞产生几乎所有类型的成熟血细胞,包括成人型β-珠蛋白表达红细胞和类胰蛋白酶/糜蛋白酶双阳性肥大细胞。这些祖细胞既没有表现出ESC的不成熟特性,也没有在克隆水平分化成内胚层和外胚层的潜力。hESC共培养体系的建立为细胞治疗和药物筛选提供了新的造血细胞和血细胞来源。
We propose a novel method for the efficient production of hematopoietic progenitors from human embryonic stem cells (hESC) via coculture with murine fetal liver-derived stromal cells, in which embryonic hematopoiesis dramatically expands at midgestation. We generated various hematopoietic progenitors in coculture, and this hematopoietic activity was concentrated in cobblestone-like cells derived from differentiated hESC. The cobblestone-like cells mostly expressed CD34 and retained an endothelial cell potential. They also contained hematopoietic colony-forming cells, especially erythroid and multilineage colony-forming cells at high frequency. The multipotential hematopoietic progenitors abundant among the cobblestone-like cells produced almost all types of mature blood cells, including adult-type beta-globin-expressing erythrocytes and tryptase/chymase double-positive mast cells. These progenitors showed neither the immature properties of ESC nor the potential to differentiate into endoderm and ectoderm at a clonal level. ne coculture system developed for hESC can provide a novel source of hematopoietic and blood cells for applications in cellular therapy and drug screening.