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和昂贵的。最近，主办方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。这项研究的总体目标是系统地开发和表征一种体内方案，该方案包括瞬时传递软骨生成和细胞外基质(ECM)刺激因子，以使用骨髓塞进行有效的修复。1)利用兔软骨前体细胞进行聚合培养，通过瞬时联合应用软骨形成因子和细胞外基质刺激因子，确定软骨组织形成的最佳方案。2)基于Aim 1的结果，确定病毒转导成软骨细胞和ECM刺激因子基因后的转基因表达和软骨组织形成。3)研究病毒导入体外培养兔骨髓块后的转基因表达和软骨组织形成情况。4)采用兔模型，评价基因激活的骨髓凝块对体内软骨和骨软骨损伤的修复作用。

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.