MARROW STROMAL CELLS IN OSTEOGENESIS IMPERFECTA MODEL

成骨不全模型中的骨髓基质细胞

• 批准号: 6445891
• 负责人: Radhika R Pochampally
• 金额: $ 3.78万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-05 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6445891
• 关键词: SCID mouse; alleles; bone fracture; bone marrow; bone marrow transplantation; clinical research; collagen; complementary DNA; connective tissue cells; disease /disorder model; gene expression; gene mutation; gene targeting; gene therapy; genetic manipulation; genetic recombination; human tissue; mutant; nucleic acid sequence; osteogenesis imperfecta; polymerase chain reaction; positron emission tomography; procollagen; southern blotting

DESCRIPTION (provided by applicant): Osteogenesis Imperfecta (OI) that has an incidence of 1/10,000 - 1/20,000 live births, has frequently served as a model disorder for dominant negative conditions of structural proteins. Effective therapy for these disorders will require direct or targeted replacement of a mutated gene with wild-type allele. This research proposal will explore the possibility that patients with OI can potentially be treated with their own osteoprogenitors by gene-engineering the cells from their bone marrow that are referred to as mesenchymal stem cells or marrow stromal cells (MSCs). The marrow stromal cells will be used to test the hypothesis that marrow stromal cells from the patients with OI can be gene-engineered to correct the deleterious effects of mutations in type I collagen that produce the disease. The Specific Aims for this proposal are: (1) To obtain homologous recombination of the COL1A1 gene in human MSCs to determine the possibility of alleviating the OI symptoms by replacing the mutant allele with wild type allele of COL1A1 (2) To obtain over-expression clones of hMSCs that express COL1A1 cDNA to determine the effect of ratio of wild-type to mutant COL1A1 protein (3) To study the repair potential and homing of gene engineered hMSCs; the repair potential of gene engineered MSCs will be determined by injecting the cells into the fracture model and control mice.

描述（由申请人提供）：成骨不全（OI）， 发病率为1/10，000 - 1/20，000活产，经常作为结构蛋白显性阴性病症的模型病症。有效 这些疾病的治疗将需要直接或靶向地替代 具有野生型等位基因的突变基因。本研究计划将探讨 OI患者有可能用自己的药物治疗 通过基因工程从他们的骨髓中提取细胞， 称为间充质干细胞或骨髓基质细胞（MSC）。的 骨髓基质细胞将被用来检验骨髓基质细胞 来自成骨不全患者的细胞可以通过基因工程来纠正 导致疾病的I型胶原蛋白突变的有害影响。 本研究的具体目的是：（1）获得同源重组 COL 1A 1基因在人骨髓间充质干细胞，以确定减轻的可能性， 通过用COL 1A 1的野生型等位基因替换突变等位基因来治疗OI症状 (2)为了获得表达COL 1A 1 cDNA的hMSC的过表达克隆， 确定野生型与突变型COL 1A 1蛋白的比例的影响（3） 研究基因工程hMSCs的修复能力和归巢能力， 基因工程MSC的潜力将通过注射细胞来确定 骨折模型和对照组小鼠。