Multistage Adipose-Derived Stem Cell Myogenesis: An Experimental and Modeling Study
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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.
KeywordsAdipose-derived stem cell Myogenesis Dynamic culture Uniaxial strain Kinetic stage-transition model
We would like to thank Dr. Jeffrey Gimble for providing the ASCs and Dr. Douglas DiGirolamo for use of the Flexcell system. We also thank Sue Kulason for the computational work at early stages of the project. This work was supported by Maryland Stem Cell Research Fund (2012-MSCRFF-165) and Johns Hopkins Department of Biomedical Engineering.
Conflict of Interest
Pinar Yilgor Huri, Andrew Wang, Alexander Spector, and Warren Grayson declare that they have no conflicts of interest.
Human ASCs were isolated in accordance with an Institutional Review Board approved protocol at the Stem Cell Biology Laboratory, Pennington Biomedical Research Center. No animal studies were carried out by the authors for this study.
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