Skip to main content
Journal cover image

Tissue-Engineered Human Myobundle System as a Platform for Evaluation of Skeletal Muscle Injury Biomarkers.

Publication ,  Journal Article
Khodabukus, A; Kaza, A; Wang, J; Prabhu, N; Goldstein, R; Vaidya, VS; Bursac, N
Published in: Toxicological sciences : an official journal of the Society of Toxicology
July 2020

Traditional serum biomarkers used to assess skeletal muscle damage, such as activity of creatine kinase (CK), lack tissue specificity and sensitivity, hindering early detection of drug-induced myopathies. Recently, a novel four-factor skeletal muscle injury panel (MIP) of biomarkers consisting of skeletal troponin I (sTnI), CK mass (CKm), fatty-acid-binding protein 3 (Fabp3), and myosin light chain 3, has been shown to have increased tissue specificity and sensitivity in rodent models of skeletal muscle injury. Here, we evaluated if a previously established model of tissue-engineered functional human skeletal muscle (myobundle) can allow detection of the MIP biomarkers after injury or drug-induced myotoxicity in vitro. We found that concentrations of three MIP biomarkers (sTnI, CKm, and Fabp3) in myobundle culture media significantly increased in response to injury by a known snake venom (notexin). Cerivastatin, a known myotoxic statin, but not pravastatin, induced significant loss of myobundle contractile function, myotube atrophy, and increased release of both traditional and novel biomarkers. In contrast, dexamethasone induced significant loss of myobundle contractile function and myotube atrophy, but decreased the release of both traditional and novel biomarkers. Dexamethasone also increased levels of matrix metalloproteinase-2 and -3 in the culture media which correlated with increased remodeling of myobundle extracellular matrix. In conclusion, this proof-of-concept study demonstrates that tissue-engineered human myobundles can provide an in vitro platform to probe patient-specific drug-induced myotoxicity and performance assessment of novel injury biomarkers to guide preclinical and clinical drug development studies.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Toxicological sciences : an official journal of the Society of Toxicology

DOI

EISSN

1096-0929

ISSN

1096-6080

Publication Date

July 2020

Volume

176

Issue

1

Start / End Page

124 / 136

Related Subject Headings

  • Troponin I
  • Toxicology
  • Tissue Engineering
  • Rats, Sprague-Dawley
  • Myosin Light Chains
  • Muscular Diseases
  • Muscle, Skeletal
  • Muscle Fibers, Skeletal
  • Muscle Contraction
  • Matrix Metalloproteinase 2
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Khodabukus, A., Kaza, A., Wang, J., Prabhu, N., Goldstein, R., Vaidya, V. S., & Bursac, N. (2020). Tissue-Engineered Human Myobundle System as a Platform for Evaluation of Skeletal Muscle Injury Biomarkers. Toxicological Sciences : An Official Journal of the Society of Toxicology, 176(1), 124–136. https://doi.org/10.1093/toxsci/kfaa049
Khodabukus, Alastair, Amulya Kaza, Jason Wang, Neel Prabhu, Richard Goldstein, Vishal S. Vaidya, and Nenad Bursac. “Tissue-Engineered Human Myobundle System as a Platform for Evaluation of Skeletal Muscle Injury Biomarkers.Toxicological Sciences : An Official Journal of the Society of Toxicology 176, no. 1 (July 2020): 124–36. https://doi.org/10.1093/toxsci/kfaa049.
Khodabukus A, Kaza A, Wang J, Prabhu N, Goldstein R, Vaidya VS, et al. Tissue-Engineered Human Myobundle System as a Platform for Evaluation of Skeletal Muscle Injury Biomarkers. Toxicological sciences : an official journal of the Society of Toxicology. 2020 Jul;176(1):124–36.
Khodabukus, Alastair, et al. “Tissue-Engineered Human Myobundle System as a Platform for Evaluation of Skeletal Muscle Injury Biomarkers.Toxicological Sciences : An Official Journal of the Society of Toxicology, vol. 176, no. 1, July 2020, pp. 124–36. Epmc, doi:10.1093/toxsci/kfaa049.
Khodabukus A, Kaza A, Wang J, Prabhu N, Goldstein R, Vaidya VS, Bursac N. Tissue-Engineered Human Myobundle System as a Platform for Evaluation of Skeletal Muscle Injury Biomarkers. Toxicological sciences : an official journal of the Society of Toxicology. 2020 Jul;176(1):124–136.
Journal cover image

Published In

Toxicological sciences : an official journal of the Society of Toxicology

DOI

EISSN

1096-0929

ISSN

1096-6080

Publication Date

July 2020

Volume

176

Issue

1

Start / End Page

124 / 136

Related Subject Headings

  • Troponin I
  • Toxicology
  • Tissue Engineering
  • Rats, Sprague-Dawley
  • Myosin Light Chains
  • Muscular Diseases
  • Muscle, Skeletal
  • Muscle Fibers, Skeletal
  • Muscle Contraction
  • Matrix Metalloproteinase 2