Implantable microfluidic device for the formation of three-dimensional vasculature by human endothelial progenitor cells
Implantable microfluidic device for the formation of three-dimensional vasculature by human endothelial progenitor cells
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DOI：
10.1007/s12257-014-0021-9
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发表时间：
2014-06-01
影响因子：
3.2
通讯作者：
Lee, Jun Hyup
中科院分区：
文献类型：
--
作者：
Kim, Jin;Yang, Kisuk;Lee, Jun Hyup
血管发生是血管组织工程和缺血性疾病治疗的重要形态发生事件。干细胞和祖细胞可以通过内皮分化和直接参与血管形成来促进血管发生。在这项研究中，我们开发了一种可植入的微流控装置，以促进形成三维（3D）血管结构的人内皮祖细胞（hEPCs）。微流控装置由可生物降解的聚（乳酸-共-乙醇酸）（PLGA）制成，使用微通道图案化的硅晶片通过软光刻制成。含有hEPCs的I型胶原（Col I）水凝胶填充微流体通道以重建3D微环境，用于促进hEPCs形成血管结构。将接种有hEPCs的装置植入无胸腺小鼠的皮下空间，并在植入后1周和4周取回。组织学和免疫组织化学显示，hEPCs在PLGA微流控装置的通道中形成表达内皮细胞特异性蛋白的3D毛细血管网络。这一结果表明，在微通道中重建的三维微尺度细胞外基质可以促进hEPCs的内皮分化，进而促进hEPCs介导的血管发生。本文报道的PLGA微流体装置可用作血管化组织重建和治疗性血管生成的可植入组织工程支架。
Vasculogenesis is an important morphogenetic event for vascular tissue engineering and ischemic disease treatment. Stem and progenitor cells can contribute to vasculogenesis via endothelial differentiation and direct participation in blood vessel formation. In this study, we developed an implantable microfluidic device to facilitate formation of three-dimensional (3D) vascular structures by human endothelial progenitor cells (hEPCs). The microfluidic device was made of biodegradable poly(lactic-co-glycolic acid) (PLGA) using a microchannel patterned silicon wafer made by soft lithography. A collagen type I (Col I) hydrogel containing hEPCs filled the microfluidic channels to reconstitute a 3D microenvironment for facilitating vascular structure formation by hEPCs. The device seeded with hEPCs was implanted into the subcutaneous space of athymic mice and retrieved one and four weeks after implantation. Histology and immunohistochemistry revealed that hEPCs formed a 3D capillary network expressing endothelial cell-specific proteins in the channel of the PLGA microfluidic device. This result indicates that a 3D microscale extracellular matrix reconstituted in the microchannel can promote the endothelial differentiation of hEPCs and in turn hEPC-mediated vasculogenesis. The PLGA microfluidic device reported herein may be useful as an implantable tissue-engineering scaffold for vascularized tissue reconstruction and therapeutic angiogenesis.