A combined hiPSC-derived endothelial cell and in vitro microfluidic platform for assessing biomaterial-based angiogenesis.
A combined hiPSC-derived endothelial cell and in vitro microfluidic platform for assessing biomaterial-based angiogenesis.
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DOI：
10.1016/j.biomaterials.2018.11.032
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发表时间：
2019-02
期刊：
影响因子：
14
通讯作者：
Sylvia L Natividad-Diaz;Shane Browne;A. Jha;Zhen Ma;S. Hossainy;Yosuke K. Kurokawa;S. George;K. Healy
中科院分区：
文献类型：
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作者：
Sylvia L Natividad-Diaz;Shane Browne;A. Jha;Zhen Ma;S. Hossainy;Yosuke K. Kurokawa;S. George;K. Healy
人诱导多能干细胞 (hiPSC) 衍生的血管生成模型为患者特定平台提供了独特的机会，以研究血管生成的复杂过程以及特定微环境中内皮细胞对生物材料和生物物理变化的反应。我们提出了一种使用单一基础培养基将 hiPSC 分化为 CD31+内皮细胞群 (hiPSC-EC) 的精细方法，从多能性到分化的最后阶段。该方案产生的内皮细胞在纯化后的测定中具有功能能力。随后，通过将 hiPSC-EC 封装到可调节的生长因子隔离透明质酸 (HyA) 基质中，开发了体外血管生成模型，在基质中它们形成稳定的毛细血管样网络，对环境刺激做出反应。在设计用于研究血管生成的微流体装置中使用荧光珠证明了网络的灌注。 hiPSC-EC、仿生水凝胶和微流体平台的结合创建了一个独特的测试平台，用于快速评估血管生成生物材料的性能。
Human induced pluripotent stem cell (hiPSC) derived angiogenesis models present a unique opportunity for patient-specific platforms to study the complex process of angiogenesis and the endothelial cell response to biomaterial and biophysical changes in a defined microenvironment. We present a refined method for differentiating hiPSCs into a CD31+endothelial cell population (hiPSC-ECs) using a single basal medium from pluripotency to the final stage of differentiation. This protocol produces endothelial cells that are functionally competent in assays following purification. Subsequently, anin vitroangiogenesis model was developed by encapsulating the hiPSC-ECs into a tunable, growth factor sequestering hyaluronic acid (HyA) matrix where they formed stable, capillary-like networks that responded to environmental stimuli. Perfusion of the networks was demonstrated using fluorescent beads in a microfluidic device designed to study angiogenesis. The combination of hiPSC-ECs, bioinspired hydrogel, and the microfluidic platform creates a unique testbed for rapidly assessing the performance of angiogenic biomaterials.