Biomimetic aorta-gonad-Mesonephros-on-a-Chip to study human developmental hematopoiesis.
Biomimetic aorta-gonad-Mesonephros-on-a-Chip to study human developmental hematopoiesis.
复制标题
仿生主动脉-性腺-中肾芯片用于研究人类发育造血作用。
DOI：
10.1007/s10544-020-00488-2
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Torisawa YS4,5.
中科院分区：
文献类型：
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作者：
Sugimura R1;Ohta R1;Mori C2;Li A1;Mano T1;Sano E2;Kosugi K2;Nakahata T1;Niwa A1;Saito MK3;Torisawa YS4,5.
造血干细胞和祖细胞衍生的一个基本限制是对人类发育造血的不精确理解。在此，我们建立了一个多层微流控主动脉-性腺-中肾（AGM）芯片来模拟多能干细胞的发育性造血。该装置由两层微通道组成，微通道由半透膜隔开，允许人类造血内皮细胞（HE）和基质细胞以生理相关的空间排列共同培养，以复制AGM的结构。来源于人诱导多能干细胞（hiPSCs）的HE细胞被培养在顶部通道的间充质间质细胞层上，血管内皮细胞被共同培养在微流控装置内膜的底部。我们发现，与常规悬浮培养相比，这种芯片上的agm能有效地从hipsc中获得内皮到造血转化（EHT）。间充质间质和内皮细胞的存在使体外造血干细胞具有功能。我们建议AGM-on-a-chip可以作为一个平台来剖析人类发育造血的细胞和分子机制。
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.