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Novel Tissue Engineered Tubular Heart Tissue for In Vitro Pharmaceutical Toxicity Testing

Published online by Cambridge University Press:  16 July 2007

Jessica L. Franchini ,
John T. Propst ,
Gerald R. Comer  and
Michael J. Yost
Jessica L. Franchini
Affiliation:
Department of Surgery, University of South Carolina School of Medicine, Columbia, South Carolina 29209, USA
John T. Propst
Affiliation:
Department of Surgery, University of South Carolina School of Medicine, Columbia, South Carolina 29209, USA
Gerald R. Comer
Affiliation:
Department of Surgery, University of South Carolina School of Medicine, Columbia, South Carolina 29209, USA
Michael J. Yost
Affiliation:
Department of Surgery, University of South Carolina School of Medicine, Columbia, South Carolina 29209, USA
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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 of in vivo pharmaceutical 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 an in 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.

Keywords

artificial myocardiumtissue engineeringtoxicity screening toolconnexin caspase 3 stainingapoptosis
Type
BIOLOGICAL APPLICATIONS
Information
Microscopy and Microanalysis , Volume 13 , Issue 4 , August 2007 , pp. 267 - 271
Copyright
© 2007 Microscopy Society of America

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References

REFERENCES

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 3A4 gene. Drug Metab Dispos 34, 1650–1657.Google Scholar
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.
Hayes, A.W., Thomas, J.A. & Gardner, D.E. (2001). Cardiovascular Toxicology: Target Organ Toxicology Series. 3rd ed. London: Taylor and Francis.
Nave, B.T., Becker, M., Roenicke, V. & Henkel, T. (2002). Validation of targets and drug candidates in an engineered three-dimensional cardiac tissue model. Drug Disc Today 7, 419–425.Google Scholar
Padmanabhan, M. & Mainzen-Prince, P.S. (2006). S-allylcysteine ameliorates isoproterenol-induced cardiac toxicity in rats by stabilizing cardiac mitochondrial and lysosomal enzymes. Life Sci 80, 972–978.Google Scholar
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 electrical stimulation of cardiac myocytes cultured on scaffolds. Proc Natl Acad Sci, USA 101, 18129–18134.Google Scholar
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 the composition and orientation of extracellular matrix. J Cell Physiol 161, 89.Google Scholar
Takahashi, R., Oda, Y., Tanaka, K., Morishima, H.O., Inoue, K. & Asada, A. (2006). Epinephrine increases the extracellular lidocaine concentration in the brain: A possible mechanism for increased central nervous system toxicity. Anesthesiology 105, 984–989.Google Scholar
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 vertebrate genome after exposure to camptothecin. DNA Repair 5, 1307–1316.Google Scholar
Yost, M.J., Baicu, C.F., Stonerock, C.E., Goodwin, R.L. & Terracio, L. (2004). A novel tubular scaffold for cardiovascular tissue engineering. Tissue Eng 10, 573.Google Scholar
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 muscle construct. Circ Res 90, 223–230.Google Scholar