Novel Tissue Engineered Tubular Heart Tissue forIn VitroPharmaceutical Toxicity Testing
Source abstract
Abstract
A growing problem in cardiac drug toxicity has been blamed on the lack of adequate testing prior to authorization for prescription use. This study offers an effective alternative to the current method ofin vivopharmaceutical testing, which is time and cost prohibitive. We have accomplished this by developing the novel three-dimensional heart tube model. At the “heart” of our model lies our patented collagen scaffold that enables the cardiac myocytes to display anin vivo–like architecture. The cardiac myocytes were cocultured with the collagen tube for a period of 5 weeks, resulting in the heart tubes. Our heart tubes were treated with specific drugs (nifedipine, isoproterenol, and lidocaine) at varying concentrations. The percent of apoptotic cells was calculated based on observing the number of cells that labeled positive for caspase-3 via confocal microscopy. All three drugs exhibited negative effects at high concentrations in that the number of living cells decreased. Lidocaine showed an increase in apoptosis at concentrations of 75 μM and above. This may indicate that certain drugs have a minimum concentration level that must be reached before the cells experience apoptosis from the toxic levels.
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Research context
OpenAlex topics: Tissue Engineering and Regenerative Medicine · Electrospun Nanofibers in Biomedical Applications · 3D Printing in Biomedical Research
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (11)
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1. Yost, M.J. , Baicu, C.F. , Stonerock, C.E. , Goodwin, R.L. & Terracio, L. (2004).A novel tubular scaffold for cardiovascular tissueengineering.Tissue Eng 10,573.10.1089/107632704322791916 ↗
2. Zimmermann, W.H. , Schneiderbanger, K. , Schubert, P. , Didié, M. , Můnzel, F. , Heubach, J.F. , Kostin, S. , Neuhuber, W.L. & Eschenhagen, T. (2002).Tissue engineering of a differentiated cardiac muscleconstruct.Circ Res 90,223–230.10.1161/hh0202.103644 ↗
3. Padmanabhan, M. & Mainzen-Prince, P.S. (2006).S-allylcysteine ameliorates isoproterenol-induced cardiac toxicityin rats by stabilizing cardiac mitochondrial and lysosomal enzymes.Life Sci 80,972–978.
4. Nave, B.T. , Becker, M. , Roenicke, V. & Henkel, T. (2002).Validation of targets and drug candidates in an engineeredthree-dimensional cardiac tissue model.Drug Disc Today 7,419–425.10.1016/S1359-6446(02)02212-2 ↗
5. Simpson, D.G. , Terracio, L. , Terracio, M. , Price, R.L. , Turner, D.C. & Borg, T.K. (1994).Modulation of cardiac myocyte phenotype in vitro by thecomposition and orientation of extracellular matrix.J Cell Physiol 161,89.10.1002/jcp.1041610112 ↗
6. Hayes, A.W. , Thomas, J.A. & Gardner, D.E. (2001).Cardiovascular Toxicology: Target Organ Toxicology Series.3rd ed. London:Taylor and Francis.
7. Daugherty, A. , Herrington, D. , Greenland, P. , Roberts, H. & Taubert, K.A. (2005, March).American Heart Association addresses use of pain medications.Journal Report. www.americanheart.org.
8. Radisic, M. , Park, H. , Shing, H. , Consi, T. , Schoen, F.J. , Langer, R. , Freed, L.E. & Vunjak-Novackovic, G. (2004).Functional assembly of engineered myocardium by electricalstimulation of cardiac myocytes cultured on scaffolds.Proc Natl Acad Sci, USA 101,18129–18134.10.1073/pnas.0407817101 ↗
9. Yoshimura, A. , Nishino, K. , Takezawa, J. , Tada, S. , Kobayashi, T. , Sonoda, E. , Kawamoto, T. , Takeda, S. , Ishii, Y. , Yamada, K. , Enomoto, T. & Seki, M. (2006).A novel Rad18 function involved in protection of the vertebrategenome after exposure to camptothecin.DNA Repair 5,1307–1316.10.1016/j.dnarep.2006.05.045 ↗
10. Chen, J. , Yang, X.X. , Huang, M. , Hu, Z.P. , He, M. , Duan, W. , Chan, E. , Sheu, F.S. , Chen, X. & Zhou, S.F. (2006).Small interfering RNA-mediated silencing of cytochrome P450 3A4gene.Drug Metab Dispos 34,1650–1657.10.1124/dmd.106.009837 ↗
11. Takahashi, R. , Oda, Y. , Tanaka, K. , Morishima, H.O. , Inoue, K. & Asada, A. (2006).Epinephrine increases the extracellular lidocaine concentration inthe brain: A possible mechanism for increased central nervous systemtoxicity.Anesthesiology 105,984–989.10.1097/00000542-200611000-00020 ↗