Gene-activated Bone Marrow Plugs for Cartilage Repair

用于软骨修复的基因激活骨髓塞

• 批准号: 7707313
• 负责人: Ryan Michael Porter
• 金额: $ 1.86万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-23 至 2009-03-22
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7707313
• 关键词: Addendum; Address; Animals; Aspirate substance; Autologous; Binding; Biocompatible; Bone Marrow; Cartilage; Cartilage Matrix; Cell Communication; Cell Differentiation process; Cells; Chondrocytes; Chondrogenesis; Classification; Clinic; Coagulation Process; Complementary DNA; Complex; Cultured Cells; Data; Defect; Depth; Development; Disease; Drug Formulations; Evaluation; Extracellular Matrix; Fellowship; Fibrocartilages; Firefly Luciferases; Future; Gene Transfer; Genes; Goals; Green Fluorescent Proteins; Implant; In Situ; In Vitro; Individual; Institution; Insulin-Like Growth Factor I; Intervention; Kinetics; Laboratories; Learning; Marrow; Measures; Mesenchymal Stem Cells; Methods; Modeling; Names; New Zealand; Orthopedics; Oryctolagus cuniculus; Protocols documentation; Published Comment; Rate; Relative (related person); Research; Reservations; Site; Stem cells; Techniques; Technology; Testing; Thinking; Time; Tissue Engineering; Tissues; Training; Transforming Growth Factors; Transgenes; Type II Procollagen; Viral; Work; articular cartilage; base; bone morphogenetic protein 2; career; clinical application; design; experience; gene therapy; improved; in vivo; interest; mathematical model; monolayer; morphogens; next generation; osteochondral tissue; promoter; repaired; response to injury; scaffold; transduction efficiency; transgene expression; uptake; vector; vector-induced

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.

描述（由申请人提供）：目前涉及离体细胞培养的关节软骨修复策略已被证明复杂且昂贵。最近，申办方实验室提出了一种原位方法，利用凝固的自体骨髓填充软骨缺损，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，该方案涉及瞬时递送软骨形成和细胞外基质（ECM）刺激因子，用于使用骨髓塞进行有效修复。将解决以下具体目标：1）使用聚集体培养物中的兔软骨祖细胞，以鉴定通过软骨形成和ECM刺激因子的瞬时共施用形成软骨组织的最佳方案。2)基于目标1的结果，确定在将软骨形成和ECM刺激因子cDNA病毒递送至软骨祖细胞后的转基因表达和软骨组织形成。3)表征病毒递送至体外培养的兔骨髓栓后的转基因表达和软骨组织形成。4)利用兔模型，评价基因激活骨髓凝块修复体内软骨和骨软骨缺损的效果。

项目成果

Interleukin-1beta and tumor necrosis factor alpha inhibit chondrogenesis by human mesenchymal stem cells through NF-kappaB-dependent pathways.

白介素-1beta和肿瘤坏死因子α通过NF-kappab依赖性途径抑制人间质干细胞的软骨发生。

• DOI: 10.1002/art.24352
• 发表时间: 2009-03
• 期刊: ARTHRITIS AND RHEUMATISM
• 作者: Wehling, N.;Palmer, G. D.;Pilapil, C.;Liu, F.;Wells, J. W.;Mueller, P. E.;Evans, C. H.;Porter, R. M.
• 通讯作者: Porter, R. M.

Osteogenic potential of reamer irrigator aspirator (RIA) aspirate collected from patients undergoing hip arthroplasty.

从接受髋关节置换术的患者身上收集的扩孔器冲洗吸引器 (RIA) 抽吸物的成骨潜力。

• DOI: 10.1002/jor.20715
• 发表时间: 2009
• 期刊: Journal of orthopaedic research : official publication of the Orthopaedic Research Society
• 作者: Porter,RyanM;Liu,Fangjun;Pilapil,Carmencita;Betz,OliverB;Vrahas,MarkS;Harris,MitchelB;Evans,ChristopherH
• 通讯作者: Evans,ChristopherH