Novel tissue engineered tubular heart tissue for in vitro pharmaceutical toxicity testing.
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 microM 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.
Franchini
Jessica L
JL
Department of Surgery, University of South Carolina School of Medicine, Columbia, South Carolina 29209, USA.
Propst
John T
JT
Comer
Gerald R
GR
Yost
Michael J
MJ
D000826:Animal Testing Alternatives / Q000379:methods; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000032:analysis; D003094:Collagen; D007545:Isoproterenol / Q000494:pharmacology; D008012:Lidocaine / Q000494:pharmacology; D018613:Microscopy, Confocal; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D023822:Tissue Engineering / Q000379:methods*; D018675:Toxicity Tests / Q000379:methods*; D015262:Xenobiotics / Q000494:pharmacology*
D015262:Xenobiotics; D003094:Collagen; D008012:Lidocaine; D053148:Caspase 3; D009543:Nifedipine; D007545:Isoproterenol