In situ tissue regeneration - chemokine triggered cellular and molecular response of human mesenchymal stem cells

原位组织再生-趋化因子触发人间充质干细胞的细胞和分子反应

• 批准号: 72148255
• 负责人: Professor Dr. Michael Sittinger
• 金额: --
• 依托单位: Tissue Engineering Laboratory (CCM)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/72148255?language=en
• 关键词: situ; tissue; regeneration; chemokine; triggered

Several chemokines have the potential to chemoattract bone marrow mesenchymal stem cells (MSC). Based on in situ heart and brain tissue repair studies, and on own results, we hypothesize that a cell therapy approach using chemokines will allow the in situ recruitment of MSC to sites of damaged or arthritic diseased cartilage, and their subsequent use for the directed regeneration of it. This approach comprises supportive bio-scaffolds and bioactive molecules promoting recruitment and chondrogenesis of MSC. Our research objective is to characterize chemokine triggered cellular and molecular responses of human bone marrow MSC. This includes proteomics of the chemokine secretion profile of cartilage and chondrocytes derived from normal donors (ND) and patients with osteoarthritis (OA), study of the chemotactic effect of selected chemokines on MSC, and chemokine receptor blocking with receptor specific antibodies and siRNA. Gene expression profiling will be performed to analyze the signalling network triggered by chemokines. To study the influence of a controlled chemoattractant release on MSC, a release system will be generated and applied in nude mice. This investigation will contribute to the establishment of a chemokine based in situ regeneration of tissues such as injured or OA diseased cartilage.

几种趋化因子具有趋化骨髓间充质干细胞（MSC）的潜力。基于在原位心脏和脑组织修复的研究，并在自己的结果，我们假设，使用趋化因子的细胞治疗方法将允许在原位招募MSC受损或关节炎病变软骨的网站，并随后用于定向再生it.This方法包括支持生物支架和生物活性分子促进招聘和软骨形成的MSC。我们的研究目的是表征趋化因子触发的人骨髓MSC的细胞和分子反应。这包括来自正常供体（ND）和骨关节炎（OA）患者的软骨和软骨细胞的趋化因子分泌谱的蛋白质组学，所选趋化因子对MSC的趋化作用的研究，以及用受体特异性抗体和siRNA阻断趋化因子受体。将进行基因表达谱分析，以分析趋化因子触发的信号网络。为了研究受控的化学引诱物释放对MSC的影响，将产生释放系统并应用于裸鼠。这项研究将有助于建立一种基于趋化因子的组织原位再生，如受伤或OA患病的软骨。