Towards genetically designed tissues for regenerative medicine

Abstract

Integration of fundamental research, elucidating cell differentiation of synthetically designed trigger-inducible promoters and of viral transduction technology, is the basis of tissue engineering for regenerative medicine [29]. Fundamental research has revealed numerous factors that play a role in targeted cell differentiation, such as bone morphogenetic proteins, BMPs [37], angiogenesis-related factors (VEGF, angiopoietin [71]) or cell-cycle regulators (cyclindependent kinase inhibitors [10]). These proteins can be introduced efficiently and safely into various cell types through the development of viral vectors, which are most commonly derived from adeno- and retroviruses [74]. However, as in small-moleculebased medicine, the dose of the therapeutic agent (i.e., the transgene) differentiates a poison from a remedy (Paracelsus, 1493-1541), thereby necessitating genetic tools for adjustment of the transgene expression levels into the therapeutic window. To achieve this, a variety of adjustable expression systems have been designed and have proven essential in almost all fields of mammalian cell technology including functional genomics [23], gene therapy [74], tissue engineering [73], drug discovery [2, 88], synthetic biology [32, 36] as well as the manufacturing of protein therapeutics [6, 13]. This chapter provides an overview of current inducible expression systems with a special focus on systems suitable for tissue engineering applications. Together with an overview of currently used viral vectors this chapter explains how the discovered proteins can be applied in gene-based tissue engineering for regenerative medicine. © 2009 Springer Berlin Heidelberg.