Synthetic Mesenchymal Stem Cell Niches for Vascular Therapy

用于血管治疗的合成间充质干细胞生态位

• 批准号: 10238173
• 负责人: Wei Tan
• 金额: $ 65.57万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10238173
• 关键词: 3-Dimensional; Address; Adhesions; Anti-Inflammatory Agents; Antioxidants; Arteriovenous fistula; Autologous; Biochemical; Biocompatible Materials; Biological; Blood Circulation; Blood Vessels; Blood flow; Caliber; Cells; Chemical Structure; Clinic; Clinical; Country; Cues; Custom; Devices; Dialysis procedure; End stage renal failure; Endothelial Cells; Endothelium; Environment; Failure; Functional disorder; Future; Goals; Grant; Health; Hemodialysis; Human; Incidence; Inflammation; Lead; Left; Legal patent; Mechanics; Medial; Mesenchymal Stem Cells; Morbidity - disease rate; Natural regeneration; Nude Rats; Outcome; Oxidative Stress; Patient Rights; Patients; Production; Research; Serum; Signal Transduction; Smooth Muscle Myocytes; Stenosis; Structure; Swine Diseases; Testing; Time; Tissues; Toxin; Tube; Tubular formation; Uremia; Vascular Graft; Veins; aged; arteriovenous graft; base; cell regeneration; clinical care; design; economic cost; effective therapy; endothelial dysfunction; endothelial regeneration; improved; mimetics; mortality; non-compliance; novel; personalized care; porcine model; precision medicine; prevent; public health relevance; regenerative; stem cell differentiation

Project Summary A huge and unmet clinical need is associated with hemodialysis vascular access dysfunction, which is currently considered to be one of the most challenging forms of clinical vascular grafting. The high failure rates associated with all types of dialysis vascular access, including arteriovenous fistulae and arteriovenous graft, result in significant morbidity, mortality and economic cost. Despite the magnitude of this clinic problem, no effective solutions are available. The end-stage renal disease and other health conditions of hemodialysis patients present a hostile milieu, such as uremia, inflammation and flow disturbance caused by small and/or non-compliant vessel, around the vascular access, which account for, at least partially, the access failure. The central hypothesis for this proposal is that precision cell niches, developed under hemodialysis-relevant conditions and when applied to the clinical setting of dialysis vascular access, prevent dialysis access failure. To test this hypothesis, we will introduce cell-protective, regenerative signals in the precision cell niches, which functionalize mesenchymal stem cells (MSCs) to override the hostile milieu impact and orchestrate the arterial regeneration, leading to patent, robust vascular access. This project will use our novel biomaterials platform, which allows both the cell niche and the niche-containing structure to be tailored using clinical inputs such as uremia, blood flow, vessel compliance and diameter, with a goal of optimizing targeted arterial regeneration to reduce access failure. To pursue the research goal, three aims are proposed here. AIM 1 focuses on incorporating the precision cell niches into a peri-vascular wrap and determining its effect on the arterialization of arteriovenous fistula under simulated hemodialysis conditions. AIM 2 seeks to establish and spatially integrate distinct precision cell niche designs to promote arteriovenous graft arterialization. AIM 3 will evaluate how the precision niche design can assist MSC-based arterial regeneration for vascular access in a diseased swine model. If successful, the precision vascular access platforms developed here could transform traditional clinical care paradigms for dialysis vascular access. We envision that in the near future, nephrologists could have the access to a range of vascular access devices derived from precision cell niche designs.

项目摘要 血液透析血管通道功能障碍是巨大而未满足的临床需求，这是 目前被认为是临床血管嫁接最具挑战性的形式之一。高故障率 与所有类型的透析血管通道相关，包括动静脉瘘和动静脉移植 在明显的发病率，死亡率和经济成本中。尽管有这个诊所问题的幅度，但无效 解决方案可用。出现血液透析患者的末期肾脏疾病和其他健康状况 由小和/或不符合船只引起的敌对环境，例如尿毒症，炎症和流动障碍 在血管访问周围，至少部分地解释了访问故障。中心假设 该建议是，在血液透析相关条件下开发的精确细胞壁ni，当应用于 透析血管进入的临床环境，防止透析通道失败。为了检验这一假设，我们将 在精密细胞壁ches中引入细胞保护，再生信号，该信号功能化间质茎 细胞（MSC）覆盖敌对环境的影响并策划动脉再生，从而获得专利， 强大的血管通道。该项目将使用我们新颖的生物材料平台，该平台既可以允许细胞利基市场和 使用尿e​​mia，血流，血管依从性等临床输入来量身定制的含小众结构 和直径，目的是优化靶向动脉再生以减少访问失败。 为了实现研究目标，这里提出了三个目标。 AIM 1专注于合并精确单元 壁ches进入血管周期，并确定其对动脉瘘动脉化的影响 模拟血液透析条件。 AIM 2旨在建立和空间整合不同的精度细胞生态位 设计以促进动静脉移植动脉化。 AIM 3将评估精​​确的利基设计如何 在患病的猪模型中，协助基于MSC的动脉再生进行血管通道。如果成功， 这里开发的精密血管通道平台可以改变传统的临床护理范例 透析血管通道。我们设想，在不久的将来，肾脏科医生可以访问一系列 源自精密细胞利基设计的血管通道设备。