Engineered Stem Cell Microenvironments for controlled Vasculogenesis

描述（由申请人提供）：一种基于血管再生细胞疗法的新兴和革命性的血管疾病治疗方法，可以通过将干细胞或祖细胞递送到受损组织或血管，潜在地修复它们或形成新的组织或血管来提供长期解决方案。聚焦于人多能干细胞（hPSC）的研究，即人胚胎干细胞（hESC）和人诱导多能干细胞（hiPSC），已经深入了解了这些细胞用于血管再生的潜力，并帮助确定了参与血管发生和血管生成的关键分子事件。聚合物水凝胶已被用作研究血管网络形态发生的可调基质。我们将把我们的工作重点放在透明质酸（HA）水凝胶上，因为它能够封装细胞并提供仿生环境。 我们假设HA水凝胶可以用于提供刺激hPSC的血管衍生物的管形成和微血管网络组装的关键线索，并且这种微血管系统可以快速并入局部血管微通道中并使局部实质细胞群具有功能性营养网络。具体目标是：（1）从hiPSC中获得功能性EC和v-SMC，（2）研究用于血管形态发生的响应性HA水凝胶，和（3）使用卵内血管生成模型分析血管网络功能

DESCRIPTION (provided by applicant): An emerging and revolutionary treatment for vascular diseases based on cell therapy for vascular regeneration could provide long-term solutions by delivering stem or progenitor cells to the impaired tissues or blood vessels, potentially repairing them or forming new ones. Studies focusing on human pluripotent stem cells (hPSCs), i.e. human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), have provided insight into the potential of these cells for vascular regeneration and helped identify key molecular events involved in vasculogenesis and angiogenesis. Polymeric hydrogel have been utilized as a tunable matrix to study vascular network morphogenesis. We will focus our work on hyaluronic acid (HA) hydrogels, due to the ability to encapsulate cells and provide a biomimetic environment. We hypothesize that HA hydrogels can be employed to provide critical cues that stimulate tube formation and microvascular network assembly from vascular derivatives of hPSCs, and that such microvasculature can be rapidly incorporated into local vascular microchannels and invest local parenchymal cell populations with functional nutrient networks. The specific aims are: (1) To Derive Functional ECs and v-SMCs from hiPSCs, (2) To Study Responsive HA Hydrogels for Vascular Morphogenesis, and (3) To Analyze Vascular Network Functionality using an In Ovo Angiogenesis Model