Organ-on-Chip: A synthetic mimic for human myocardium

Berend van Meer, Marcelo Ribeiro, Leon Tertoolen, Matthew Birket, Robert Passier, Christine Mummery

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Abstract

Current drug testing methodology still fails to identify high-risk side effects, one third of which are related to cardiotoxicity, despite strict regulatory protocols. Apart from drugs withdrawn after FDA approval, 9 out of 10 experimental drugs already fail in Phase I clinical trials. These are strong indications that the animal models used in drug development do not accurately predict the effects of drugs on humans. Therefore, it is of utmost importance to develop new, humanized heart models that are accurate.

Human pluripotent stem cell (hPSC) derived cardiovascular cells could provide new tools for more reliable drug screening and as such, they could serve as an accurate alternative for animal models. Moreover, human Induced Pluripotent Cells (hiPSC) allow modelling of human genetic diseases since these can be obtained by reprogramming somatic cells of adult patients.

In this research, a non-invasive measurement setup is being developed that optically assesses the membrane potential, calcium flux and force of contraction simultaneously in a single cell. The biophysical parameters are each sampled with a frequency of 333 Hz, allowing accurate evaluation of most important parameter values and kinetics. This provides a starting point to integrate the multiplexed measurement assays with a heterogeneous tissue population and engineered scaffold technology to create a synthetic mimic for myocardium, resulting in a so called “Organ-on-Chip”-model. Furthermore, with the use of hiPSC, genetic cardiac disease models can be made to use in drug development, reducing the use of animal models and increasing the efficiency of pharmaceutical drug discovery trajectories.
Original languageEnglish
Article number0176
Pages (from-to)388-388
JournalJournal of Pharmacological and Toxicological Methods
Volume81
DOIs
Publication statusPublished - 2016
Externally publishedYes

Keywords

  • n/a OA procedure

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