Open AccessDoxorubicin‐induced cardiomyocyte toxicity – protective effects of endothelial cells in a tri‐culture model system
Author(s) -
Alias Eliesmaziah,
Parikh Vijay,
HidalgoBastida Araida,
Wilkinson Malcolm,
Davidge Kelly S.,
Gibson Tim,
Sharp Duncan,
Shakur Rameen,
Azzawi May
Publication year - 2018
Publication title -
journal of interdisciplinary nanomedicine
Language(s) - English
Resource type - Journals
ISSN - 2058-3273
DOI - 10.1002/jin2.42
Subject(s) - cardiotoxicity , doxorubicin , in vivo , in vitro , pharmacology , toxicity , medicine , troponin , cancer research , chemotherapy , chemistry , biology , biochemistry , microbiology and biotechnology , myocardial infarction
Doxorubicin‐induced cardiomyopathy is a clinically prevalent pathology, occurring as a sequelae following chemotherapy for cancer patients. In particular, the “first dose” effect has been particularly challenging, given the heterogeneous and multifactorial nature of this pathophysiology. Here, we describe the development of a physiologically relevant in vitro model for cardiotoxicity testing, using human cells. Primary cardiomyocytes, endothelial, and smooth muscle cells were tri‐cultured in 2D, or within nano‐fibrous scaffolds in a 3D environment, under dynamic nutrient flow, using the Quasi Vivo® system. State‐of‐the‐art sensor chips were used to detect troponin I levels, 2 h after acute exposure to doxorubicin. We demonstrate a significant improvement in cardiomyocyte viability when grown in a 3D tri‐culture environment over a 5‐day period and a 10‐fold reduction in doxorubicin‐induced toxicity. Our tri‐culture model can be used as a valuable tool for physiologically relevant assessment of drug‐induced cardiotoxicity in vitro.