Drug-screening Platform Based on the Contractility of Tissue-Engineered Muscle

Muscle Nerve. 2008 Apr;37(4):438-47. doi: 10.1002/mus.20931.

Abstract

A tissue-based approach to in vitro drug screening allows for determination of the cumulative positive and negative effects of a drug at the tissue rather than the cellular or subcellular level. Skeletal muscle myoblasts were tissue-engineered into three-dimensional muscle with parallel myofibers generating directed forces. When grown attached to two flexible micro-posts (mu posts) acting as artificial tendons in a 96-well plate format, the miniature bioartificial muscles (mBAMs) generated tetanic (active) forces upon electrical stimulation measured with a novel image-based motion detection system. mBAM myofiber hypertrophy and active force increased in response to insulin-like growth factor 1. In contrast, mBAM deterioration and weakness was observed with a cholesterol-lowering statin. The results described in this study demonstrate the integration of tissue engineering and biomechanical testing into a single platform for the screening of compounds affecting muscle strength.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Atorvastatin
  • Biological Assay / instrumentation
  • Biological Assay / methods*
  • Cells, Cultured
  • Drug Evaluation, Preclinical / instrumentation
  • Drug Evaluation, Preclinical / methods*
  • Electric Stimulation
  • Heptanoic Acids / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Insulin-Like Growth Factor I / pharmacology
  • Male
  • Mice
  • Mice, Inbred C3H
  • Muscle Contraction / drug effects*
  • Muscular Atrophy / drug therapy*
  • Muscular Atrophy / physiopathology
  • Myoblasts / cytology
  • Myoblasts / drug effects
  • Pyrroles / pharmacology
  • Tissue Engineering / instrumentation
  • Tissue Engineering / methods*

Substances

  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Insulin-Like Growth Factor I
  • Atorvastatin