Transgenic human tissue: a powerful new tool for research and therapeutic targeting.

组织工程是一种快速发展的医学技术，它使用人类细胞和特殊材料在实验室中创造出活的人体组织或器官。这种组织可以用来修复患者的病变或受损组织。目前的例子包括骨、皮肤、软骨和膀胱；但希望有一天也能创造出更复杂的组织和器官，减少对器官移植的需求。我们已经将这项技术与基因治疗相结合，创造出了能够抵抗关节炎破坏性过程的转基因软骨。这样的组织在修复这些患者的软骨方面可能更有效。在这项技术的基础上，但加入了被称为“RNA干扰”的新技术，我们现在处于一个独特的位置来创造人类组织，在其中任何特定的蛋白质都可以被“敲除”。这种组织有可能成为一种强大的研究工具，可以用来确定任何分子在正常或疾病人类组织中的作用。近年来，这项任务在很大程度上是由转基因小鼠完成的。然而，生产这种“转基因”动物可能是有争议的，而且也是昂贵和耗时的。更重要的是，动物模型并不总是正确地反映人类的情况。这项研究计划的目的是创造新型的人类转基因组织工程软骨，并证明它可以用作确定哪些特定分子参与关节炎组织破坏的模型。这对设计治疗这种疾病的特效药应该大有裨益。这项技术在软骨中的成功应用应该同样适用于其他工程组织，如骨和皮肤，并可能具有极大的科学和治疗价值。

Tissue engineering is a rapidly advancing medical technique that uses human cells and specialised materials to create living human tissues or organs in the laboratory. Such tissue can be used to repair diseased or damaged tissues in patients. Current examples of this include bone, skin, cartilage and bladder; however it is hoped that more complex tissues and organs will one day also be created, decreasing the demand for organ transplantation. We have combined this technology with that of gene therapy to create genetically modified cartilage that is resistant to the destructive processes of arthritis. Such tissue may be more effective in repairing cartilage in these patients. Based on this technique, but incorporating new technology known as 'RNA interference' we are now in a unique position to create human tissue in which any specific protein can be 'knocked-out'. This tissue has the potential to be a powerful research tool that could be used to determine the role of any molecule in normal or diseased human tissues. In recent years this task has, to a large extent, been fulfilled by genetically engineered mice. However production of such 'transgenic' animals can be controversial and is also expensive and time consuming. More importantly, animal models do not always correctly reflect the situation in humans. The aim of this research proposal is to create novel human transgenic tissue engineered cartilage and demonstrate that it can be used as a model to determine which specific molecules are involved in tissue destruction in arthritis. This should be of great benefit in designing specific drugs for the treatment of this disease. Successful application of this technology in cartilage should be equally applicable to other engineered tissues such as bone and skin and could be of great scientific and therapeutic interest.