Engineered Stem Cell Microenvironments for controlled Vasculogenesis

用于控制血管生成的工程干细胞微环境

基本信息

批准号：
8675921
负责人：
Sharon Gerecht
金额：
$ 44.86万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8675921
关键词：
Address Adhesions Adverse effects Affect Beds Biocompatible Materials Biological Assay Biology Biomedical Engineering Biomimetics Blood Vessels Blood flow Bone Marrow Cell Proliferation Cell Therapy Cells Chick Embryo Cues Developmental Biology Disease Embryonic Development Encapsulated Endothelial Cells Engineering Environment Event Extracellular Matrix Fibroblasts Future Heart failure Human Human Engineering Hyaluronic Acid Hydrogels Implant In Vitro Ischemia Kinetics Lead Limb structure Mechanics Modeling Molecular Morphogenesis Natural regeneration Nutrient Organ Outcome Pathway Analysis Patients Pharmacologic Substance Pluripotent Stem Cells Population Procedures Process Protocols documentation Rattus Regulation Research Role Signal Transduction Smooth Muscle Myocytes Solutions Source Stem cells Stroke Structure Three-dimensional analysis Tissues Transplantation Tube Vascular Diseases Work angiogenesis base chorioallantoic membrane clinical application cytokine human embryonic stem cell implantation in vivo induced pluripotent stem cell insight prevent repaired stem subcutaneous vasculogenesis

项目摘要

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

描述（由申请人提供）：基于血管再生细胞疗法的一种新兴的革命性血管疾病治疗方法可以通过将干细胞或祖细胞输送到受损的组织或血管，潜在地修复它们或形成新的组织或血管，从而提供长期的解决方案。关注人类多能干细胞 (hPSC)，即人类胚胎干细胞 (hESC) 和人类诱导多能干细胞 (hiPSC) 的研究深入了解了这些细胞的血管再生潜力，并帮助识别了血管生成中涉及的关键分子事件和血管生成。聚合物水凝胶已被用作可调谐基质来研究血管网络形态发生。我们将把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 水凝胶可用于提供刺激 hPSC 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纳入局部血管微通道，并为局部实质细胞群提供功能性营养网络。具体目标是：(1) 从 hiPSC 衍生功能性 EC 和 v-SMC，(2) 研究用于血管形态发生的响应性 HA 水凝胶，以及 (3) 使用卵内血管生成模型分析血管网络功能