Tissue Engineering a Skeletal Muscle Model of Type 2 Diabetes

One of the major challenges in muscle tissue engineering is to fabricate and develop a tissue engineered skeletal muscle construct (TE-SkM) that is representative of the structure and metabolic function of native skeletal muscle. For example, in diabetes, there is a great need to develop TE-SkM models that can predict the structural and physiological changes occurring in vivo, to find new possible targets to treat this disease. Based on these premises, the purpose of this research project was to develop and characterize a novel diabetic tissue engineered skeletal muscle model (TE-SkM) that effectively incorporates important components of diabetic skeletal muscle, namely fat and microvessels. Primarily, the hypothesis behind this project was that the inclusion of these components would enable the generation of a model that could be physiologically relevant for studying diabetes. The research has been subdivided into three aims focused on studying the possible interactions between muscle precursor cells (MPCs), adipocytes, and microvessels. MPCs from both lean and diabetic rats were used in this project to create healthy and diabetic TE-SkM constructs, respectively. Specifically, the vascular component was introduced by using microvascular fragments, while the inclusion of fat was achieved by promoting the adipogenic differentiation of MPCs. Overall, the strategy proved to be successful in integrating all the three components into a physiologically relevant in vitro model. This strategy could potentially be used to study the mechanism responsible for diminished angiogenesis and fat infiltration in SkM during diabetes and other metabolic conditions.