Engineered Stem Cell Microenvironments for controlled Vasculogenesis

用于控制血管生成的工程干细胞微环境

• 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
• 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

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(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提供长期解决方案，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。对人类多能干细胞(HPSCs)，即人胚胎干细胞(HESCs)和人诱导多能干细胞(HiPSCs)的研究，有助于深入了解这些细胞在血管再生方面的潜力，并有助于识别参与血管生成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。由于透明质酸(HA)水凝胶能够包裹细胞并提供仿生环境，我们将把工作重点放在HA水凝胶上。我们假设HA水凝胶可以提供关键信号，刺激hPSCs的血管衍生物形成微血管网络，并且这种微血管可以迅速整合到局部血管微通道中，并使局部实质细胞群具有功能的营养网络。具体目标是：(1)从HiPSCs中分离出具有功能的内皮细胞和v-SMC；(2)研究用于血管形态发生的响应性HA水凝胶；(3)利用体内血管生成模型分析血管网络的功能