Engineered Human Muscle Tissue from Multilayered Aligned Myofiber Sheets for Studies of Muscle Physiology and Predicting Drug Response

Hironobu Takahashi, Haruno Wakayama, Kenichi Nagase, Tatsuya Shimizu

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

In preclinical drug testing, human muscle tissue models are critical to understanding the complex physiology, including drug effects in the human body. This study reports that a multilayering approach to cell sheet-based engineering produces an engineered human muscle tissue with sufficient contractile force suitable for measurement. A thermoresponsive micropatterned substrate regulates the biomimetic alignment of myofiber structures enabling the harvest of the aligned myofibers as a single cell sheet. The functional muscle tissue is produced by layering multiple myofiber sheets on a fibrin-based gel. This gel environment promotes myofiber maturation, provides the tissue an elastic platform for contraction, and allows the attachment of a measurement device. Since this multilayering approach is effective in enhancing the contractile ability of the muscle tissue, this muscle tissue generates a significantly high contractile force that can be measured quantitatively. The multilayered muscle tissue shows unidirectional contraction from electrical and chemical stimulation. In addition, their physiological responses to representative drugs can be determined quantitatively in real time by changes in contractile force and fatigue resistance. These physiological properties indicate that the engineered muscle tissue can become a promising tissue model for preclinical in vitro studies in muscle physiology and drug discovery.

Original languageEnglish
Article number2200849
JournalSmall Methods
Volume7
Issue number2
DOIs
Publication statusPublished - 2023 Feb 17

Keywords

  • cell sheets
  • contractile force
  • drug testing
  • fatigue resistance
  • muscle tissue engineering
  • tissue anisotropy
  • tissue models

ASJC Scopus subject areas

  • General Chemistry
  • General Materials Science

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