Bosworth Allison M, Faley Shannon L, Bellan Leon M, Lippmann Ethan S
Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, United States.
Department of Mechanical Engineering, Vanderbilt University, Nashville, TN, United States.
Front Bioeng Biotechnol. 2018 Jan 30;5:87. doi: 10.3389/fbioe.2017.00087. eCollection 2017.
The neurovascular unit (NVU) is composed of neurons, astrocytes, pericytes, and endothelial cells that form the blood-brain barrier (BBB). The NVU regulates material exchange between the bloodstream and the brain parenchyma, and its dysfunction is a primary or secondary cause of many cerebrovascular and neurodegenerative disorders. As such, there are substantial research thrusts in academia and industry toward building NVU models that mimic endogenous organization and function, which could be used to better understand disease mechanisms and assess drug efficacy. Human pluripotent stem cells, which can self-renew indefinitely and differentiate to almost any cell type in the body, are attractive for these models because they can provide a limitless source of individual cells from the NVU. In addition, human-induced pluripotent stem cells (iPSCs) offer the opportunity to build NVU models with an explicit genetic background and in the context of disease susceptibility. Herein, we review how iPSCs are being used to model neurovascular and neurodegenerative diseases, with particular focus on contributions of the BBB, and discuss existing technologies and emerging opportunities to merge these iPSC progenies with biomaterials platforms to create complex NVU systems that recreate the microenvironment.
神经血管单元（NVU）由神经元、星形胶质细胞、周细胞和内皮细胞组成，这些细胞共同构成血脑屏障（BBB）。NVU调节血液与脑实质之间的物质交换，其功能障碍是许多脑血管疾病和神经退行性疾病的主要或次要原因。因此，学术界和工业界都在大力开展研究，致力于构建能够模拟内源性组织和功能的NVU模型，以更好地理解疾病机制并评估药物疗效。人类多能干细胞能够无限自我更新并分化为体内几乎任何细胞类型，因此对这些模型具有吸引力，因为它们可以提供NVU单个细胞的无限来源。此外，人类诱导多能干细胞（iPSC）为构建具有明确遗传背景且与疾病易感性相关的NVU模型提供了机会。在此，我们综述了iPSC如何用于模拟神经血管疾病和神经退行性疾病，特别关注血脑屏障的作用，并讨论了将这些iPSC后代与生物材料平台相结合以创建能够重现微环境的复杂NVU系统的现有技术和新出现的机会。
