Abstract
Transdifferentiation of human non-muscle cells directly into myogenic cells by forced expression of MyoD represents one route to obtain highly desirable human myogenic cells. However, functional properties of the tissue constructs derived from these transdifferentiated cells have been rarely studied. Here, we report that three-dimensional (3D) tissue constructs engineered with iMyoD-hTERT-NHDFs, normal human dermal fibroblasts transduced with genes encoding human telomerase reverse transcriptase and doxycycline-inducible MyoD, generate detectable contractile forces in response to electrical stimuli upon MyoD expression. Withdrawal of doxycycline in the middle of 3D culture results in 3.05 and 2.28 times increases in twitch and tetanic forces, respectively, suggesting that temporally-controlled MyoD expression benefits functional myogenic differentiation of transdifferentiated myoblast-like cells. Treatment with CHIR99021, a Wnt activator, and DAPT, a Notch inhibitor, leads to further enhanced contractile forces. The ability of these abundant and potentially patient-specific and disease-specific cells to develop into functional skeletal muscle constructs makes them highly valuable for many applications, such as disease modeling.
Original language | English (US) |
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Article number | 22047 |
Journal | Scientific reports |
Volume | 10 |
Issue number | 1 |
DOIs | |
State | Published - Dec 2020 |
Bibliographical note
Funding Information:We thank Prof. Robert T. Tranquillo for the use of the contractile force measurement apparatus. We thank Prof. Louis Mansky for the use of the Zeiss LSM 700 confocal laser scanning microscope. This work was supported by the National Science Foundation (CAREER DMR-1151529 for W.S.) and by Institute for Engineering in Medicine at the University of Minnesota.
Publisher Copyright:
© 2020, The Author(s).