The University of Southampton

Monitoring contractility of bio-realistic human cardiac tissue in vitro

Date:
2014-2014
Theme:
Bionanotechnology and Biosensors
Funding:
NC3Rs

Animals are currently needed to perform cardiac pharmacology and toxicology studies on novel compounds with potential therapeutic value before their use in clinical practice. A potential alternative is the use of human stem cell-derived cardiac cells but, with the current culture protocols, they present poorly developed features of adult cardiac cells and therefore are inadequate for drug testing. Here, we aim to develop a novel, in vitro system consisting of cell culture platforms with special structural and mechanical properties designed to encourage maturation of human stem cell-derived cardiomyocytes into tissues with relevant structure and physiology. These platforms will allow the use of a simple method to monitor cardiac contractility, a frequent target of cardiac and non-cardiac drugs that is currently difficult to monitor in toxicology settings. In order to obtain the maturation of the stem cell-derived cardiac cells, we will engineer flexible membranes using Parylene-C, a biocompatible and durable polymer, already used for other bioengineering purposes. The novel application of this material consists in the fabrication of very thin membranes to be used as a cell culture substrate. As adult cardiac tissue is formed by elongated, carefully aligned cells, the cell culture membranes will be patterned to obtain the deposition of the cells into parallel lines. This will be achieved by oxygen plasma treatment, a technique that makes the membrane differentially hydrophilic in predetermined areas, allowing adhesion of the cells only in certain configurations. In these conditions the cells will develop a shape and structure that is more similar to mature cardiac cells. To study contractility we will develop an optical system and associated software for a reproducible and reliable image movement analysis. This method will be incorporated in an existing system developed for the screening of large number of compounds and used in combination with other techniques, to provide a comprehensive assessment of the response to drug treatment. If successful this system will also be employed for studies into the mechanisms of cardiac disease, with further, significant reduction of the use of animals for research.

Associated research group

  • Nano Research Group
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