Drug-screening platform based on the contractility of tissue-engineered muscle.
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.
Vandenburgh
Herman
H
Department of Pathology, RISE Research Building, Brown Medical School/Miriam Hospital, Providence, RI 02906, USA. herman_vandenburgh@brown.edu
Shansky
Janet
J
Benesch-Lee
Frank
F
Barbata
Victoria
V
Reid
Jonathan
J
Thorrez
Lieven
L
Valentini
Robert
R
Crawford
Gregory
G
D000818:Animals; D000069059:Atorvastatin; D001681:Biological Assay / Q000295:instrumentation / Q000379:methods*; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation / Q000379:methods*; D004558:Electric Stimulation; D006538:Heptanoic Acids / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009119:Muscle Contraction / Q000187:drug effects*; D009133:Muscular Atrophy / Q000188:drug therapy* / Q000503:physiopathology; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D007334:Insulin-Like Growth Factor I; D000069059:Atorvastatin