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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

基本信息

批准号：
10461011
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
项目类别：
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/10461011
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 Chemicals 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 Vascular regeneration 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

项目摘要

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.

项目总结