High-throughput, real-time monitoring of engineered skeletal muscle function using magnetic sensing

Author:

Smith Alec ST12ORCID,Luttrell Shawn M3,Dupont Jean-Baptiste24,Gray Kevin3,Lih Daniel3,Fleming Jacob W3,Cunningham Nathan J3,Jepson Sofia5,Hesson Jennifer26,Mathieu Julie26,Maves Lisa7,Berry Bonnie J3,Fisher Elliot C3,Sniadecki Nathan J258ORCID,Geisse Nicholas A3,Mack David L1259

Affiliation:

1. Department of Physiology and Biophysics, University of Washington, Seattle, WA, USA

2. Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA

3. Curi Bio Inc., 3000 Western Avenue, Seattle, WA, USA

4. Nantes Université, INSERM, TARGET, Nantes, France

5. Department of Bioengineering, University of Washington, Seattle, WA, USA

6. Department of Comparative Medicine, University of Washington, Seattle, WA, USA

7. Seattle Children’s Research Institute, Seattle, WA, USA

8. Department of Mechanical Engineering, University of Washington, Seattle, WA, USA

9. Department of Rehabilitation Medicine, University of Washington, Seattle, WA, USA

Abstract

Engineered muscle tissues represent powerful tools for examining tissue level contractile properties of skeletal muscle. However, limitations in the throughput associated with standard analysis methods limit their utility for longitudinal study, high throughput drug screens, and disease modeling. Here we present a method for integrating 3D engineered skeletal muscles with a magnetic sensing system to facilitate non-invasive, longitudinal analysis of developing contraction kinetics. Using this platform, we show that engineered skeletal muscle tissues derived from both induced pluripotent stem cell and primary sources undergo improvements in contractile output over time in culture. We demonstrate how magnetic sensing of contractility can be employed for simultaneous assessment of multiple tissues subjected to different doses of known skeletal muscle inotropes as well as the stratification of healthy versus diseased functional profiles in normal and dystrophic muscle cells. Based on these data, this combined culture system and magnet-based contractility platform greatly broadens the potential for 3D engineered skeletal muscle tissues to impact the translation of novel therapies from the lab to the clinic.

Funder

National Institutes of Health

Publisher

SAGE Publications

Subject

Biomedical Engineering,Biomaterials,Medicine (miscellaneous)

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