Engineered Stem Cell Microenvironments for controlled Vasculogenesis

用于控制血管发生的工程干细胞微环境

基本信息

批准号：
8086942
负责人：
Sharon Gerecht
金额：
$ 39.95万
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/8086942
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 PUBLIC HEALTH RELEVANCE: 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. We will utilize polymeric hydrogel as a three-dimensional milieu to generate microvasculature bed from human pluripotent stem cells. Our study will provide a profound analysis of 3D human vascular network formation and functionality, and overall relevance of these vascular networks in future clinical applications.

描述（由申请人提供）：基于细胞治疗血管再生的血管疾病的新兴和革命治疗可以通过将茎或祖细胞输送到受损的组织或血管中，从而提供长期溶液，从而有可能修复或形成新的溶液。侧重于人多能干细胞（HPSC），即人类胚胎干细胞（HESC）和人诱导的多能干细胞（HIPSC）的研究为这些细胞对血管再生的潜力提供了见识，并帮助鉴定了与血管生成有关的关键分子事件和血管生成。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。由于能够封装细胞并提供仿生环境，我们将把工作重点放在透明质酸（HA）水凝胶上。我们假设可以利用HA水凝胶来提供关键的提示，从而刺激HPSC的血管衍生物的管形成和微血管网络组装，并且可以将这种微血管造成迅速纳入局部血管微通道中，并将其投资于具有功能性营养网络的局部实质性细胞群中。具体目的是：（1）从HIPSC中得出功能性EC和V-SMC，（2）研究血管形态发生的反应性HA水凝胶，（3）使用OVO血管生成模型分析血管网络功能公共卫生相关性：基于细胞治疗血管再生的血管疾病的新兴和革命治疗方法可以通过将茎或祖细胞输送到受损的组织或血管中，从而提供长期溶液，从而有可能修复或形成新的溶液。我们将利用聚合物水凝胶作为三维环境来产生人类多能干细胞的微脉管床。我们的研究将对3D人血管网络形成和功能以及这些血管网络在未来的临床应用中的总体相关性提供深入的分析。