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This article reviews some of the recent findings resulting from tissue engineering …

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Engineering skeletal muscle tissue
- Skeletal muscle tissue engineering

The engineering of muscle tissue in vitro holds promise for the treatment of skeletal muscle defects as an alternative to host muscle transfer [1, 3, 4, 18, 19]. Skeletal muscle tissue engineering depends on the regenerative properties of the satellite cells and their potential for proliferation and differentiation, since these primary skeletal muscle cells can be harvested from adult muscle and successfully grown in vitro [15, 20]. Important requirements of engineering functional skeletal muscle are a parallel alignment of myofibrils with myosin/actin filaments, intracelluar calcium-strorage and acetylcholin receptors, which are needed for creating direct forces and functional use. Besides the neotissue must be biocompatible, needs to be vascularised and finally needs to be innervated [5, 21]. In order to obtain large volumes of tissue engineered skeletal muscle, myoblast cell cultures need to be expanded to a great extend. However, with extending passaging of primary cells, the differentiation process is difficult to induce. To overcome these problems in many studies focussing on in vitro generation of muscular tissue cell lines such as C2C12 which is an established cell line of satellite cells from skeletal muscle of C3H mouse, were used [22–25]. However this approach seems to have disadvantages, because established cell lines approxi-the replacement of muscular tissues using tissue mate myogenesis less closely than primary engineering methods have only recently started and myoblasts. Therefore primary cultures derived from many investigators have focussed on the creation of satellite cells from myofibers grown in vitro are the functional muscle tissues in vitro [23, 28, 29]. preferred source of myoblasts because they recapit-However, few studies on differentiation of ulate muscle development more precisely than myoblasts within a 3-D matrix have been reported immortal myogenic cell lines [5, 26, 27]. Studies on and living tissue substitutes for functional skeletal muscle replacement have not yet been developed successfully. To achieve this goal it is necessary to investigate novel approaches for culturing functional, differentiated skeletal muscle tissue in vitro using primary myoblasts for autologous transplantation. An understanding of the molecular control mechanisms of muscle development and differentiation is therefore an important prerequisite. It is becoming apparent that the circumstances related to the growth of cells in three-dimensional scaffolds in vitro are revealing aspects of the phenotypes of cells and insights into cell behaviors that would have otherwise escaped view. In this regard skeletal muscle tissue engineering has become a general model for understanding many fundamental principles of development, including mechanisms for cell differentiation, morphogenesis and the antagonism between growth and differentiation [30, 31]. Many of the steps involved in the development of myoblasts from mesodermal precursor cells and their subsequent differentiation into multinucleate muscle fibers correspond to the expression of specific transcription factors and signalling systems controlling each developmetal event. The factors which play a major role in controlling the events leading to skeletal muscle development are MyoD, myf-5, myogenin and myf-6/MRF4/herculin, a family of myogenic basic helix-loop-helix transcription factors [32-34]. The proper spatial and temporal expression of these transcription factors is critical for successful myogenesis [32].


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