Department of Anatomy and Embryology, Leiden University Medical Center, the Netherlands.
BIOS Lab-on-a-Chip group, University of Twente, the Netherlands; Applied Stem Cell Technologies group, University of Twente, the Netherlands.
Adv Drug Deliv Rev. 2019 Feb 1;140:68-77. doi: 10.1016/j.addr.2018.06.007. Epub 2018 Jun 23.
The vascular system is one of the first to develop during embryogenesis and is essential for all organs and tissues in our body to develop and function. It has many essential roles including controlling the absorption, distribution and excretion of compounds and therefore determines the pharmacokinetics of drugs and therapeutics. Vascular homeostasis is under tight physiological control which is essential for maintaining tissues in a healthy state. Consequently, disruption of vascular homeostasis plays an integral role in many disease processes, making cells of the vessel wall attractive targets for therapeutic intervention. Experimental models of blood vessels can therefore contribute significantly to drug development and aid in predicting the biological effects of new drug entities. The increasing availability of human induced pluripotent stem cells (hiPSC) derived from healthy individuals and patients have accelerated advances in developing experimental in vitro models of the vasculature: human endothelial cells (ECs), pericytes and vascular smooth muscle cells (VSMCs), can now be generated with high efficiency from hiPSC and used in 'microfluidic chips' (also known as 'organ-on-chip' technology) as a basis for in vitro models of blood vessels. These near physiological scaffolds allow the controlled integration of fluid flow and three-dimensional (3D) co-cultures with perivascular cells to mimic tissue- or organ-level physiology and dysfunction in vitro. Here, we review recent multidisciplinary developments in these advanced experimental models of blood vessels that combine hiPSC with microfluidic organ-on-chip technology. We provide examples of their utility in various research areas and discuss steps necessary for further integration in biomedical applications so that they can be contribute effectively to the evaluation and development of new drugs and other therapeutics as well as personalized (patient-specific) treatments.
脉管系统是胚胎发生过程中最早发育的系统之一，对我们体内所有器官和组织的发育和功能至关重要。它具有许多重要的功能，包括控制化合物的吸收、分布和排泄，因此决定了药物和治疗剂的药代动力学。血管稳态受严格的生理控制，这对于维持组织的健康状态至关重要。因此，血管稳态的破坏在许多疾病过程中起着重要作用，使血管壁细胞成为治疗干预的有吸引力的靶标。因此，血管的实验模型可以为药物开发做出重大贡献，并有助于预测新药物实体的生物学效应。越来越多的来自健康个体和患者的人诱导多能干细胞（hiPSC）的可用性加速了开发血管实验体外模型的进展：现在可以从 hiPSC 高效地生成人内皮细胞（ECs）、周细胞和血管平滑肌细胞（VSMCs），并将其用于“微流控芯片”（也称为“器官芯片”技术）作为血管体外模型的基础。这些接近生理的支架允许受控的流体流动和与周细胞的三维（3D）共培养的整合，以模拟组织或器官水平的生理学和体外功能障碍。在这里，我们综述了将 hiPSC 与微流控器官芯片技术相结合的这些先进血管实验模型的最新多学科进展。我们提供了它们在各种研究领域中的应用实例，并讨论了在生物医学应用中进一步整合所需的步骤，以便它们能够有效地为新药物和其他治疗剂的评估和开发以及个性化（患者特异性）治疗做出贡献。
