Gene-Augmented Mesenchymal Stem Cells in Bone Repair

基因增强间充质干细胞在骨修复中的应用

• 批准号: 6792398
• 负责人: TERRI A ZACHOS
• 金额: $ 6.38万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6792398
• 关键词: Adenoviridae; articular cartilage; biological signal transduction; biotechnology; bone fracture; bone morphogenetic proteins; bone regeneration; bone transplantation; cartilage development; cartilage transplantation; collagen; femur fracture; gene delivery system; gene therapy; joints; knee; laboratory mouse; mesenchyme; nonhuman therapy evaluation; orthopedics; postdoctoral investigator; protein structure function; stainings; stem cell transplantation; transcription factor; transfection; transfection /expression vector; western blottings

DESCRIPTION (provided by applicant): The healing of fractures involving bone and articular cartilage poses significant clinical challenge and socioeconomic impact. Numerous factors may impair healing of fractures, particularly those involving joints. It is estimated that 10-15% of 6.5 million fractures occurring annually will not heal. The elderly are more severely impacted and have greater morbidity associated with resulting osteoarthritis. Gene transfer in combination with bone marrow-derived mesenchymal stem cells (BMDMSC), which are pluripotent, can allow for controlled production of transgene products at desired sites, however, studies have not evaluated healing in fractures involving joints. Our goal is to identify the roles of bone morphogenetic proteins (BMPs) in BMDMSC during fracture healing, using an adenoviral delivery system. We will create an articular fracture in the distal femur of mice, implant BMP gene-transfected BMDMSC, and measure molecular signals associated with the rate and integrity of fracture repair. We hypothesize that gene delivery of two different BMPs will result in accelerated healing of fractures, but by different mechanisms, confirmed by the production of unique cartilage- and bone-specific messages.

描述（由申请人提供）：涉及骨骼和关节软骨的裂缝的愈合会带来重大的临床挑战和社会经济影响。许多因素可能会损害裂缝的愈合，尤其是涉及关节的裂缝。据估计，每年发生的650万骨折中有10-15％无法治愈。老年人受到更严重的影响，并具有更大的发病率与导致的骨关节炎有关。与多能的基因转移与骨髓来源的间充质干细胞（BMDMSC）可以允许在所需部位控制转基因产物的产生，但是，研究尚未评估涉及关节的裂缝中的愈合。我们的目标是使用腺病毒递送系统确定骨折愈合过程中骨形态发生蛋白（BMP）在BMDMSC中的作用。我们将在小鼠的远端股骨，植入BMP基因转染的BMDMSC中产生关节骨折，并测量与裂缝修复速率和完整性相关的分子信号。我们假设基因递送两个不同的BMP将导致裂缝的愈合加速，但是通过不同的机制，通过产生独特的软骨和骨特异性消息证实。