Gene-Augmented Mesenchymal Stem Cells in Bone Repair

描述(由申请人提供)：涉及骨和关节软骨的骨折的愈合具有重大的临床挑战和社会经济影响。许多因素可能会影响骨折的愈合，特别是涉及关节的骨折。据估计，每年发生的650万个骨折中，有10%-15%不会愈合。老年人受到的影响更严重，与由此导致的骨关节炎相关的发病率也更高。基因转移结合骨髓间充质干细胞(BMDMSC)具有多能性，可以在所需部位控制转基因产物的产生，然而，研究尚未评估涉及关节的骨折的愈合情况。我们的目标是使用腺病毒递送系统，确定骨形态发生蛋白(BMPs)在骨折愈合过程中BMDMSC中的作用。我们将在小鼠股骨远端造成关节骨折，植入转BMP基因的BMDMSC，并测量与骨折修复速度和完整性相关的分子信号。我们假设，两种不同的BMP的基因传递将导致骨折的加速愈合，但通过不同的机制，证实了独特的软骨和骨骼特异性信息的产生。

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.