Engineering Tissue with miRNAs

描述(由申请人提供)：最近发现的microRNAs(MiRNAs)及其控制全球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活性代表了引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，将特定的miRNA模拟和抑制物转染hMSCs可以使这些细胞对骨诱导信号敏感，导致在经成骨介质处理的2D培养中更快地呈现与骨相关的标记。该项目的目标是通过测试miRNA转基因的hMSCs在合成3D支架中再生骨的能力来评估基于miRNA的策略在改进现有骨修复方法方面的潜力。这将首先通过细胞培养中构建的结构的体外测试(AIM1)完成，然后是对大鼠临界大小的骨量缺陷的体内研究(AIM2)。如果成功，该项目将展示miRNA模拟物和抑制剂的新用途，并为基于miRNA的生物医学工程技术的继续探索提供有价值的支持。 与公共卫生相关：基于干细胞的疗法正在迅速开发，以帮助组织工程师为临床应用再生骨量。如果成功，该项目将确定一种在合成3D组织支架中增强骨形成的新机制，并为继续探索基于miRNA的组织工程策略提供支持。

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.