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Biomimetic aorta-gonad-Mesonephros-on-a-Chip to study human developmental hematopoiesis.
Biomedical Microdevices ( IF 2.8 ) Pub Date : 2020-05-06 , DOI: 10.1007/s10544-020-00488-2
Ryohichi Sugimura 1 , Ryo Ohta 1 , Chihiro Mori 2 , Alina Li 1 , Takafumi Mano 1 , Emi Sano 2 , Kaori Kosugi 2 , Tatsutoshi Nakahata 1 , Akira Niwa 1 , Megumu K Saito 1 , Yu-Suke Torisawa 2, 3
Affiliation  

A fundamental limitation in the derivation of hematopoietic stem and progenitor cells is the imprecise understanding of human developmental hematopoiesis. Herein we established a multilayer microfluidic Aorta-Gonad-Mesonephros (AGM)-on-a-chip to emulate developmental hematopoiesis from pluripotent stem cells. The device consists of two layers of microchannels separated by a semipermeable membrane, which allows the co-culture of human hemogenic endothelial (HE) cells and stromal cells in a physiological relevant spatial arrangement to replicate the structure of the AGM. HE cells derived from human induced pluripotent stem cells (hiPSCs) were cultured on a layer of mesenchymal stromal cells in the top channel while vascular endothelial cells were co-cultured on the bottom side of the membrane within the microfluidic device. We show that this AGM-on-a-chip efficiently derives endothelial-to-hematopoietic transition (EHT) from hiPSCs compared with regular suspension culture. The presence of mesenchymal stroma and endothelial cells renders functional HPCs in vitro. We propose that the AGM-on-a-chip could serve as a platform to dissect the cellular and molecular mechanisms of human developmental hematopoiesis.

中文翻译:

仿生主动脉-性腺间充质干细胞研究人类发育性造血功能。

造血干细胞和祖细胞衍生的基本限制是对人类发育造血功能的不精确理解。在这里,我们建立了一个芯片上的多层微流体主动脉-性腺-中肾(AGM),以模拟来自多能干细胞的造血功能。该设备由两层微通道组成,这两层微通道由半透膜隔开,该膜允许在生理相关的空间安排中共同培养人血源性内皮细胞(HE)和基质细胞,以复制AGM的结构。将源自人诱导性多能干细胞(hiPSC)的HE细胞培养在顶部通道的间充质基质细胞层中,而将血管内皮细胞共培养在微流控设备膜的底部。我们显示,与常规悬浮培养相比,此AGM-on-a-chip芯片可有效地从hiPSCs衍生内皮细胞向造血细胞的过渡(EHT)。间充质基质和内皮细胞的存在使体外功能性HPCs。我们建议,芯片上的AGM可以作为一个平台来解剖人类发育造血的细胞和分子机制。
更新日期:2020-05-06
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