Efficient Differentiation of Human Pluripotent Stem Cells to Endothelial Cells.
Efficient Differentiation of Human Pluripotent Stem Cells to Endothelial Cells.
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DOI：
10.1002/cphg.64
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发表时间：
2018-07
影响因子：
--
通讯作者：
Gu M
中科院分区：
文献类型：
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作者：
Gu M
内皮细胞（Endothelial cells，EC）位于血管和淋巴管的内表面，在血栓形成、炎症、血管壁重塑等多种生理或病理过程中发挥着重要作用。人诱导多能干细胞（iPSC）衍生的EC为血管再生提供了新的机会，并作为研究机制和筛选新疗法的模型。我们在单层分化方法中使用发育线索，通过在化学成分确定的培养基中小分子激活WNT信号传导，以及随后使用血管内皮生长因子和成纤维细胞生长因子进行四天的EC规范，从iPSC有效地产生中胚层细胞。进一步分化8天后，使用针对EC表面标记物CD 144的磁激活细胞分选进一步纯化成熟EC。这些内皮细胞表现出与天然内皮细胞一致的分子和细胞特征，如表达特异性表面标记物、形成管状结构和乙酰化低密度脂蛋白摄取。
Endothelial cells (ECs) line the interior surface of blood and lymphatic vessels, and play a key role in a variety of physiological or pathological processes such as thrombosis, inflammation, or vascular wall remodeling. Human induced pluripotent stem cell (iPSCs)-derived ECs provide a new opportunity for vascular regeneration and serve as a model to study the mechanism and to screen for novel therapies. We use developmental cues in a monolayer differentiation approach to efficiently generate mesoderm cells from iPSCs via small-molecule activation of WNT signaling in chemically defined media, and subsequent EC specification using vascular endothelial growth factor and fibroblast growth factor for four days. After eight days of further differentiation, mature ECs are further purified using magnetic-activated cell sorting for the EC surface marker CD144. These ECs exhibit molecular and cellular characteristics consistent with native ECs, such as expression of specific surface markers, formation of tube-like structures and acetylated low-density lipoprotein uptake.