Engineered 2D & 3D hiPSC-CM platforms to detect cardiovascular safety liabilities

Safety evaluation of drugs is a costly, protracted process that requires ~500,000 procedures on rodents, rabbits, dogs and primates in the UK annually. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) could provide faster, more accurate safety testing, reducing costs and sparing thousands of animals. Because hiPSC-CM are in development, improvements are needed to integrate mature cells into platform(s) that simultaneously report on electrophysiology, calcium and contractility under (patho)physiological load.

Our unique international consortium comprises academic/SME partners with >50 person-years of expertise with stem cell-derived cardiomyocytes.

Through effective management, sponsor interaction and an established collaborative network, Phase 2 will further develop 2D, pseudo-3D and 3D platforms using cost-effective hiPSC-CM produced in-house. Cell function will be improved via advanced media, flexible substrates and cell mixing. Researcher mobility will facilitate exchange of skills in cell engineering, hardware/software design, readouts and analysis, while in-kind contributions of compounds and data from the sponsor will enhance validation. We will offer a globally-competitive portfolio of screening platforms. Our ready-made consortium will be primed for entry into EU schemes (Horizon2020, IMIs). It will bolster existing 3Rs activity that has recently won Dutch (Hugo van Poelgeest; Lef in het Lab) and German (DFG Ursula Händel Tierschutzpreis) animal reduction prizes.

Full details about this CRACK IT Challenge can be found on the CRACK IT website.

van Meer BJ, Tertoolen LGJ, Mummery CL (2016). Concise Review: Measuring Physiological Responses of Human Pluripotent Stem Cell Derived Cardiomyocytes to Drugs and Disease. Stem Cells, 34(8): 2008–2015. doi: 10.1002/stem.2403.

Mannhardt I et al, (2016). Human Engineered Heart Tissue: Analysis of Contractile Force. Stem Cell Reports, 7(1): 29–42. doi: 10.1016/j.stemcr.2016.04.011.

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CRACK IT Challenge

Award date:

Jul 2014

Contract amount

£999,915

Primary 'R'

Replacement

Scientific Discipline

Safety

Technologies/approach

In vitro techniques

Keywords

hiPS cell-derived cardiomyocytes