An In-Vivo but Non-Animal Test System for Cell Recruitment and Cell Integration into the Heart

Applications are invited for a 3-year self-funded PhD.

The PhD will be based in the Faculty of Science and Health, and will be supervised by Dr Susanne Dietrich, Dr Anthony Lewis and Dr Aikaterini Lalatsa who will combine their expertise in heart development, heart beat control and cell-supporting biomaterials.

Cardiovascular disease is the most prevalent cause of death, because it frequently leads to a fatal stroke or heart attack. In a heart attack, blood and oxygen supply to the beating heart cells becomes obstructed, and as a consequence, heart muscle cells perish.

Current efforts aim to develop therapeutic cells that can replace the lost cells and restore heart function. This however has not been achieved because exogenously generated cells fail to integrate into the framework of the existing heart and to beat in tune, causing potentially fatal arrhythmias_¹.

In the embryo, a cell population exists that is recruited and integrated into the primitive, already beating heart². How the integration of these so-called secondary heart field cells is facilitated is not known.

This project will use the chicken embryo in the egg as an in-vivo but non-animal test system for cell recruitment and cell integration into the heart. The project will first investigate, how cell recruitment and integration works. Thereafter, the project will establish whether tissue-culture-grown, potential therapeutic human cells can integrate into the primitive heart in the same fashion as the normal embryonic cells. 

To monitor cell recruitment, fluorescently labelled cells will be transplanted into the secondary heart field of early stage chicken embryos; cell contribution to the heart and cell beating will be assessed by fluorescence videomicroscopy.

To monitor cell integration, changes in marker gene expression, cell shapes and cell-to-cell contacts will be recorded, using in situ hybridisation and immunohistochemistry, alongside quantitative methods such as qPCR. There will be a particular focus on the expression of ion channels which control beating. To develop a platform for the evaluation of human cells, biomaterials will be tested for their ability to present the cells to the existing heart for recruitment³.

References

1. Scuderi, G.J. and J. Butcher, Naturally Engineered Maturation of Cardiomyocytes. Front Cell Dev Biol, 2017. 5: p. 50
2. Wittig, J.G. and A. Munsterberg, The Early Stages of Heart Development: Insights from Chicken Embryos. J Cardiovasc Dev Dis, 2016. 3(2).
3. Moshayedi, P., et al., Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain. Biomaterials, 2016. 105: p. 145–155.

Fees and funding

Funding availability: Self-funded PhD students only. 

PhD full-time and part-time courses are eligible for the UK Government Doctoral Loan (UK and EU students only).