Directed differentiation of definitive hemogenic endothelium and hematopoietic progenitors from human pluripotent stem cells
Directed differentiation of definitive hemogenic endothelium and hematopoietic progenitors from human pluripotent stem cells
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人类多能干细胞定向分化确定性造血内皮和造血祖细胞
DOI：
10.1016/j.ymeth.2015.10.001
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发表时间：
2016-05-15
期刊：
影响因子：
4.8
通讯作者：
Sturgeon, Christopher M.
中科院分区：
文献类型：
--
作者：
Ditadi, Andrea;Sturgeon, Christopher M.
从人多能干细胞（hPSC）产生造血干细胞（HSC）仍然是再生医学和疾病建模的主要目标。然而，hPSC分化培养物主要产生属于胚胎HSC非依赖性造血程序的造血祖细胞，这对于模拟正常和疾病状态的成人造血过程可能不相关或不准确。通过阶段特异性定向分化方法，现在有可能从hPSC产生专门的永久性造血祖细胞，其显示出更发育晚期的胎儿造血的特征。在这里，我们总结了最近的努力，通过在规定的条件下胚状体分化hPSC衍生的永久性造血。通过从基质胶包被的塑料器皿酶促解离hPSC，然后通过重组BMP 4，驱动中胚层特化，产生拟胚体。通过GSK 3 β-抑制剂，随后通过重组VEGF和支持性造血细胞因子来指定连续性造血。然后，使用该方法获得的CD 34（+）细胞适用于造血测定以确定造血潜能。(C)2015 Elsevier Inc. All rights reserved.
The generation of hematopoietic stem cells (HSCs) from human pluripotent stem cells (hPSCs) remains a major goal for regenerative medicine and disease modeling. However, hPSC differentiation cultures produce mostly hematopoietic progenitors belonging to the embryonic HSC-independent hematopoietic program, which may not be relevant or accurate for modeling normal and disease-state adult hematopoietic processes. Through a stage-specific directed differentiation approach, it is now possible to generate exclusively definitive hematopoietic progenitors from hPSCs showing characteristics of the more developmentally advanced fetal hematopoiesis. Here, we summarize recent efforts at generating hPSC-derived definitive hematopoiesis through embryoid body differentiation under defined conditions. Embryoid bodies are generated through enzymatic dissociation of hPSCs from matrigel-coated plasticware, followed by recombinant BMP4, driving mesoderm specification. Definitive hematopoiesis is specified by a GSK3 beta-inhibitor, followed by recombinant VEGF and supportive hematopoietic cytokines. The CD34(+) cells obtained using this method are then suitable for hematopoietic assays for definitive hematopoietic potential. (C) 2015 Elsevier Inc. All rights reserved.