Engineering Tissue with miRNAs

用 miRNA 工程组织

基本信息

批准号：
8097538
负责人：
KRISTI S. ANSETH
金额：
$ 15.84万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8097538
关键词：
3&apos Untranslated Regions 3-Dimensional Alkaline Phosphatase Attention Binding Biomedical Engineering Bone Regeneration Calcium Cell Culture Techniques Cell Fate Control Cell Therapy Cells Clinical Complex Defect Deposition Development Encapsulated Gene Expression Gene Targeting Genes Genetic Markers Goals Human Laboratories Lead Medical Mesenchymal Messenger RNA Metabolic Pathway Methods MicroRNAs Natural regeneration Nude Rats Osteogenesis Pattern Proteins RNA Processing Rattus Signal Transduction Site Speed Stem cells System Techniques Testing Therapeutic Tissue Differentiation Tissue Engineering Tissues Transfection Translations Work base bone bone mass clinical application craniofacial cranium implantation improved in vitro testing in vivo inhibitor/antagonist novel osteogenic prevent public health relevance repaired scaffold stem cell differentiation tissue support frame tool

项目摘要

DESCRIPTION (provided by applicant): The recent discovery of microRNAs (miRNAs) and their ability to control global gene expression patterns may revolutionize current tissue engineering strategies. Altering cellular miRNA activity represents a unique mechanism for directing differentiation and tissue formation. Preliminary results obtained in our lab demonstrate that the transfection of hMSCs with specific miRNA mimics and inhibitors sensitizes these cells to osteoinductive signals, causing a more rapid presentation of bone-related markers in 2D cultures treated with osteogeneic media. The goal of this project is to evaluate the potential of miRNA-based strategies for improving current bone repair methods by testing the ability of miRNA-transfected hMSCs to regenerate bone in synthetic 3D scaffolds. This will be accomplished first by in vitro testing of the constructs in cell culture (Aim1) followed by in vivo studies of critical-sized bone mass defects in rats (Aim2). If successful, this project will demonstrate a novel utility for miRNA mimics and inhibitors and provide valuable support for the continued exploration of miRNA-based biomedical engineering techniques. PUBLIC HEALTH RELEVANCE: Stem cell-based therapies are quickly being developed to help tissue engineers regenerate bone mass for clinical applications. If successful, this project will identify a novel mechanism for enhancing bone formation in synthetic 3D tissue scaffolds and provide support for continued exploration of miRNA-based strategies for engineering tissues.

描述（由申请人提供）：最近发现的 microRNA (miRNA) 及其控制全局基因表达模式的能力可能会彻底改变当前的组织工程策略。改变细胞 miRNA 活性代表了指导分化和组织形成的独特机制。我们实验室获得的初步结果表明，用特定的 miRNA 模拟物和抑制剂转染 hMSC 可使这些细胞对骨诱导信号敏感，从而在用成骨介质处理的 2D 培养物中更快地呈现骨相关标记。该项目的目标是通过测试转染 miRNA 的 hMSC 在合成 3D 支架中再生骨的能力，评估基于 miRNA 的策略在改进当前骨修复方法方面的潜力。这将首先通过细胞培养中的构建体的体外测试（Aim1）来完成，然后对大鼠的临界尺寸骨量缺陷进行体内研究（Aim2）。如果成功，该项目将展示 miRNA 模拟物和抑制剂的新用途，并为继续探索基于 miRNA 的生物医学工程技术提供宝贵支持。公共健康相关性：基于干细胞的疗法正在迅速开发，以帮助组织工程师再生骨量以用于临床应用。如果成功，该项目将确定一种增强合成 3D 组织支架中骨形成的新机制，并为继续探索基于 miRNA 的组织工程策略提供支持。