Multistage Adipose-Derived Stem Cell Myogenesis: An Experimental and Modeling Study

Adipose-derived stem/stromal cells (ASCs) possess great potential as an autologous cell source for cell-based regenerative therapies. We have previously shown that mimicking the natural dynamic muscle loading patterns enhances differentiation capacity of ASCs into aligned myotubes. In particular, the application of uniaxial cyclic strain significantly increased ASC myogenesis in monolayer cultures. In this study, we demonstrate that the temporal expression of key myogenic markers Pax3/7, Desmin, MyoD and myosin heavy chain closely mimics patterns described for muscle satellite cells. Using these lineage markers, we propose that the progression from undifferentiated ASCs to myotubes can be described as transitions through discrete stages. Based on our experimental data, we developed a compartmental kinetic stage-transition model to provide a quantitative description of the differentiation of ASCs to terminally differentiated myotubes. The model describing ASCs' myogenic differentiation in response to biophysical cues could help to obtain a deeper understanding of factors governing the biological responses and provide clues for experimental methods to increase the efficiency of ASC myogenesis for the development of improved muscle regenerative therapies.