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血管疾病的新兴和革命性治疗方法，可以通过将干细胞或祖细胞输送到受损组织或血管中，可能修复它们或形成新的组织或血管，提供长期解决方案。针对人类多能干细胞（hPSCs），即人类胚胎干细胞（hESCs）和人类诱导多能干细胞（hiPSCs）的研究，已经深入了解了这些细胞在血管再生方面的潜力，并帮助确定了参与血管生成和血管生成的关键分子事件。高分子水凝胶已被用作研究血管网络形态发生的可调基质。我们将把重点放在透明质酸（HA）水凝胶上，因为它能够包裹细胞并提供仿生环境。我们假设，透明质酸水凝胶可以提供关键线索，刺激人乳头状细胞的血管衍生物形成管和微血管网络组装，并且这种微血管可以迅速融入局部血管微通道，并为局部实质细胞群体提供功能性营养网络。具体目标是：(1)从hiPSCs中获得功能性ECs和v-SMCs，(2)研究响应性HA水凝胶用于血管形态发生，以及(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