Controlling Exosome Noncoding RNA Cargo for Enhanced Wound Healing

控制外泌体非编码 RNA 货物以增强伤口愈合

基本信息

批准号：
9907865
负责人：
Steven Michael Jay
金额：
$ 37.61万
依托单位：
UNIV OF MARYLAND, COLLEGE PARK
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-01 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9907865
关键词：
Address Biomedical Engineering Biophysics Burn injury Cell Culture Techniques Cell Density Cell Therapy Cell physiology Cells Data Development Diffusion Down-Regulation Endothelial Cells Endothelium Ethanol Excision Exposure to Financial Hardship Formulation Functional disorder Gene Expression Goals Healthcare Systems In Vitro Investigation MALAT1 gene Mediating Membrane Methodology Methods MicroRNAs Modeling Morbidity - disease rate Mus Nucleic Acids Patient Care Patients Physiological Production Regulation Rodent Rodent Model Source Surgeon Techniques Testing Therapeutic Treatment Efficacy Untranslated RNA Up-Regulation Vascularization Viral Work Wound models angiogenesis base burn wound clinical translation conditioning diabetic diabetic wound healing exosome experimental study extracellular vesicles genetic manipulation improved in vivo induced pluripotent stem cell intercellular communication nanoparticle non-healing wounds novel pH gradient preclinical study preservation prevent repaired sonoporation therapeutic evaluation three dimensional cell culture vector wound healing

项目摘要

Project Summary Exosomes have emerged as potential therapeutic vectors for repair of non-healing wounds, which continue to be a significant source of morbidity and represent a substantial financial burden to patients and health care systems in general. However, the therapeutic potency – and thus the translational potential – of exosomes for wound repair is limited, as exosomes contain low amounts of nucleic acid cargo, such as microRNAs (miRNAs), which are critical to defining exosome bioactivity. Towards overcoming this limitation, we have developed a novel ethanol conditioning approach for endothelial cell-derived exosomes. This method reduces anti- angiogenic miRNA cargo and increases pro-angiogenic long non-coding RNA cargo in these exosomes, leading to an overall increase in angiogenic bioactivity. Angiogenic dysfunction is a hallmark of non-healing wounds, thus these enhanced exosome formulations have therapeutic potential in wound repair. Our team of bioengineers and clinicians will test approaches to further exert control over endothelial exosome non-coding RNA cargo and bioactivity via environmental conditioning approaches (Aim 1) and exogenous loading techniques (Aim 2). We will further test the therapeutic efficacy of enhanced exosomes in excisional, diabetic, and burn injury wound repair models (Aim 3) to identify the most promising avenue for further translational investigations. Overall, these studies will promote the development of a new class of therapeutics for non-healing wounds that could benefit millions of patients.

项目概要外泌体已成为修复不愈合伤口的潜在治疗载体，这些伤口继续是发病率的重要来源，并对患者和医疗保健造成巨大的经济负担然而，外泌体的治疗效力以及转化潜力。伤口修复是有限的，因为外泌体含有少量的核酸货物，例如 microRNA (miRNA)，这对于定义外泌体生物活性至关重要，为了克服这一限制，我们开发了一种方法。用于内皮细胞来源的外泌体的新型乙醇调理方法该方法减少了抗- 血管生成 miRNA 货物并增加这些外泌体中促血管生成的长非编码 RNA 货物，导致血管生成生物活性的总体增加是不愈合伤口的标志，因此，这些增强的外泌体制剂在伤口修复方面具有治疗潜力。生物工程师和忠诚者将测试进一步控制内皮外泌体非编码的方法通过环境调节方法（目标 1）和外源负载实现 RNA 货物和生物活性技术（目标 2）我们将进一步测试增强的外泌体在切除、糖尿病、和烧伤伤口修复模型（目标 3）以确定最有希望的进一步转化途径总体而言，这些研究将促进新型疗法的开发。无法愈合的伤口可以使数百万患者受益。