Gene transfer in tissue repair: status, challenges and future directions

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Abstract
Wound repair involves a complex interaction of various cell types, extracellular matrix molecules and soluble mediators. Details on signals controlling wound cell activities are beginning to emerge. In recent years this knowledge has been applied to a number of therapeutic strategies in soft tissue repair. Key challenges include re-adjusting the adult repair process in order to augment diseased healing processes, and providing the basis for a regenerative rather than a reparative wound environment. In particular, the local delivery of pluripotent growth factor molecules to the injured tissue has been intensively investigated over the past decade. Limited success of clinical trials indicates that an important aspect of the growth factor wound-healing paradigm is the effective delivery of these polypeptides to the wound site. A molecular genetic approach in which genetically modified cells synthesise and deliver the desired growth factor in a time-regulated manner is a powerful means to overcome the limitations associated with the (topical) application of recombinant growth factor proteins. This article summarises repair mechanisms and their failure, and gives an overview of techniques and studies applied to gene transfer in tissue repair. It also provides perspectives on potential targets for gene transfer technology.