Gene-activated Bone Marrow Plugs for Cartilage Repair

描述（由申请人提供）：目前涉及体外细胞培养的关节软骨修复策略已被证明是复杂且昂贵的。最近，赞助实验室提出了一种原位方法，利用凝固的自体骨髓来填充软骨缺损，并为内源性修复提供生物相容性支架。本研究的总体目标是系统地开发和表征一种体内方案，该方案涉及使用骨髓塞短暂递送软骨生成和细胞外基质（ECM）刺激因子，以实现有效修复。以下具体目标将被解决：1)在聚集培养中使用兔软骨祖细胞，通过软骨生成和ecm刺激因子的短暂共同管理来确定软骨组织形成的最佳方案。2)基于目的1的结果，确定病毒向软骨祖细胞传递成软骨和ECM刺激因子cdna后的转基因表达和软骨组织形成。3)观察体外培养兔骨髓栓病毒转染后基因的表达和软骨组织的形成。4)采用家兔模型，评价基因活化骨髓凝块在体内修复软骨和骨软骨缺损的效果。

DESCRIPTION (provided by applicant): Current strategies for articular cartilage repair involving ex vivo cell culture have proven complex and expensive. Recently, the sponsor laboratory has proposed an in situ approach utilizing coagulated, autologous bone marrow to fill cartilage defects and provide a biocompatible scaffold for endogenous repair. The overall goal of this research is to systematically develop and characterize an in vivo protocol involving transient delivery of chondrogenic and extracellular matrix (ECM)-stimulating factors for effective repair using bone marrow plugs. The following specific aims will be addressed: 1) Using rabbit chondroprogenitor cells within aggregate culture, to identify an optimal protocol for cartilaginous tissue formation via transient co- administration of chondrogenic and ECM-stimulating factors. 2) Based on aim 1 results, to determine transgene expression and cartilaginous tissue formation following viral delivery of chondrogenic and ECM- stimulating factor cDNAs to chondroprogenitors. 3) To characterize transgene expression and cartilaginous tissue formation following viral delivery to rabbit marrow plugs cultured in vitro. 4) Using a rabbit model, to evaluate repair of chondral and osteochondral cartilage defects in vivo by gene-activated marrow clots.