Effect of microRNA modulation on bioartificial muscle function.
Abstract
Cellular therapies have recently employed the use of small RNA molecules, particularly
microRNAs (miRNAs), to regulate various cellular processes that may be altered in
disease states. In this study, we examined the effect of transient muscle-specific
miRNA inhibition on the function of three-dimensional skeletal muscle cultures, or
bioartificial muscles (BAMs). Skeletal myoblast differentiation in vitro is enhanced
by inhibiting a proliferation-promoting miRNA (miR-133) expressed in muscle tissues.
As assessed by functional force measurements in response to electrical stimulation
at frequencies ranging from 0 to 20 Hz, peak forces exhibited by BAMs with miR-133
inhibition (anti-miR-133) were on average 20% higher than the corresponding negative
control, although dynamic responses to electrical stimulation in miRNA-transfected
BAMs and negative controls were similar to nontransfected controls. Immunostaining
for alpha-actinin and myosin also showed more distinct striations and myofiber organization
in anti-miR-133 BAMs, and fiber diameters were significantly larger in these BAMs
over both the nontransfected and negative controls. Compared to the negative control,
anti-miR-133 BAMs exhibited more intense nuclear staining for Mef2, a key myogenic
differentiation marker. To our knowledge, this study is the first to demonstrate that
miRNA mediation has functional effects on tissue-engineered constructs.
Type
Journal articleSubject
ActininAnimals
Cell Differentiation
Cell Line
Cell Proliferation
Mice
MicroRNAs
Muscle, Skeletal
Myoblasts, Skeletal
Myosins
Tissue Engineering
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https://hdl.handle.net/10161/3365Published Version (Please cite this version)
10.1089/ten.TEA.2009.0601Publication Info
Rhim, Caroline; Cheng, Cindy S; Kraus, William E; & Truskey, George A (2010). Effect of microRNA modulation on bioartificial muscle function. Tissue Eng Part A, 16(12). pp. 3589-3597. 10.1089/ten.TEA.2009.0601. Retrieved from https://hdl.handle.net/10161/3365.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
William Erle Kraus
Richard and Pat Johnson University Distinguished Professor
My training, expertise and research interests range from human integrative physiology
and genetics to animal exercise models to cell culture models of skeletal muscle adaptation
to mechanical stretch. I am trained clinically as an internist and preventive cardiologist,
with particular expertise in preventive cardiology and cardiac rehabilitation. My
research training spans molecular biology and cell culture, molecular genetics, and
integrative human exercise physiology and metabolism. I pr
George A. Truskey
R. Eugene and Susie E. Goodson Distinguished Professor of Biomedical Engineering
My research interests focus upon the effect of physical forces on the function of
vascular cells and skeletal muscle, cell adhesion, and the design of engineered tissues.
Current research projects examine the effect of endothelial cell senescence upon
permeability to macromolecules and the response to fluid shear stress, the development
of microphysiological blood vessels and muscles for evaluation of drug toxicity and
the design of engineered endothelialized blood vessels and skelet
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