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

几种趋化因子具有吸引骨髓间充质干细胞（MSC）的潜能。基于原位心脏和脑组织修复研究，以及我们自己的结果，我们假设使用趋化因子的细胞治疗方法将允许MSC原位募集到受损或关节炎病变软骨的部位，并随后用于其定向再生。该方法包括支持性生物支架和促进间充质干细胞募集和软骨形成的生物活性分子。我们的研究目的是表征趋化因子引发的人骨髓间充质干细胞的细胞和分子反应。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，选择的趋化因子对MSC的趋化作用的研究，以及受体特异性抗体和siRNA的趋化因子受体阻断。基因表达谱将用于分析趋化因子触发的信号网络。为了研究化学引诱剂控制释放对MSC的影响，我们将制备一种释放系统并应用于裸鼠。这项研究将有助于建立一种基于原位组织再生的趋化因子，如受伤或OA病变软骨。

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.