OP9 Stroma Augments Survival of Hematopoietic Precursors and Progenitors During Hematopoietic Differentiation from Human Embryonic Stem Cells
OP9 Stroma Augments Survival of Hematopoietic Precursors and Progenitors During Hematopoietic Differentiation from Human Embryonic Stem Cells
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DOI：
10.1634/stemcells.2008-0642
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发表时间：
2008-01-01
期刊：
影响因子：
5.2
通讯作者：
Bhatia, Mickie
中科院分区：
文献类型：
--
作者：
Ji, Junfeng;Vijayaragavan, Kausalia;Bhatia, Mickie
间质微环境对多能性人胚胎干细胞（human embryonic stem cell，hESCs）造血特化的影响及其细胞机制尚未完全阐明。在这里，在相反的卵巢-性腺-中肾-衍生的S62基质细胞，OP 9细胞抑制细胞凋亡，也增加了造血前体的增殖，前瞻性地从人胚状体分离。此外，OP 9基质通过抑制定向于造血谱系的CD 45（+）CD 34（+）细胞的凋亡来支持原始造血区室中的细胞，但对更成熟的血液（CD 45（+）CD 34（+））细胞没有影响。在股内和肝内注射后，与0 P9基质细胞共培养的hESC衍生的造血细胞不能植入成年和新生NOD/SCID小鼠中，这说明尽管0 P9基质细胞增强hESC衍生的造血和祖细胞输出，但这种优化的环境不赋予或增强源自hESC的特定造血细胞的再增殖功能。0 P9共培养还增加来自过表达HOXB 4的造血前体的造血祖细胞输出。我们的研究表明，OP 9细胞支持造血前体及其原始造血后代，从而提供了第一个证据，有助于理解OP 9基质细胞支持ESC造血的能力的细胞靶点和机制，并确定实现从ESC系产生真正的人类造血干细胞的全球目标所需的未来步骤。干细胞2008; 26：2485-2495
The cellular mechanism and target cell affected by stromal microenvironments in augmenting hematopoietic specification from pluripotent human embryonic stem cells (hESCs) has yet to be evaluated. Here, in contrast to aorta-gonad-mesonephros-derived S62 stromal cells, OP9 cells inhibit apoptosis and also augment the proliferation of hemogenic precursors prospectively isolated from human embryoid bodies. In addition, OP9 stroma supported cells within the primitive hematopoietic compartment by inhibiting apoptosis of CD45(+) CD34(+) cells committed to the hematopoietic lineage, but have no effect on more mature blood (CD45(+) CD34(+)) cells. Inability of hESC-derived hematopoietic cells cocultured with OP9 stromal cells to engraft in both the adult and newborn NOD/SCID mice after intrafemoral and intrahepatic injection illustrated that although OP9 stromal cells augment hESC-derived hematopoiesis and progenitor output, this optimized environment does not confer or augment repopulating function of specified hematopoietic cells derived from hESCs. OP9 coculture also increases hematopoietic progenitors output from hemogenic precursors overexpressing HOXB4. Our study demonstrates that OP9 cells support both hemogenic precursors and their primitive hematopoietic progeny, thereby providing the first evidence toward understanding the cellular targets and mechanisms underlying the capacity of OP9 stromal cells to support hematopoiesis from ESCs and define the future steps required to achieve the global goal of generating bona fide human hematopoietic stem cells from ESC lines. STEM CELLS 2008; 26: 2485-2495