Tissue Engineering of Functional Cardiac Tissue using a Newly Characterised Cardiac Stem Cell Population

Description

We will develop a novel route to create and test stem cell-derived engineered cardiac tissue for use in heart infarct repair or in vitro drug screening.

The use of adult stem cells for the regeneration of cardiac tissue is an area of research that is growing rapidly and is of global significance. Precedent has been set with the clinical application of bone marrow-derived adult stem cells; however there is evidence that stem cells isolated from the cardiac tissue itself may provide a more relevant source for tissue engineering strategies. The aim of the research project is to investigate how biomechanical stimulation of differentiating cardiac stem cells can help to form functional cardiac tissue when combined with biomaterials formed from 3D peptide hydrogels.

The project will i) investigate how biomechanical stimulation promotes differentiation to functional cardiomyocytes, ii) optimise protocols for combining cardiac stem cells with 3D peptide hydrogels, iii) mathematically model cardiac tissue engineering and iv) investigate the efficacy of cardiac regeneration in vivo using an experimental mouse model. The project is therefore appropriate for graduates with a diverse STEM background inclusive of engineers and mathematicians with an interest in biology and biotechnology.  

Cardiac samples will be obtained through existing collaboration with cardiac surgeons at the Freeman Hospital, Newcastle. These samples will be used to harvest cardiac mesenchymal stem cells (cMSCs). Phenotypic analysis of cardiomyocyte differentiation will be analysed by expression of genes and proteins specific to the cardiomyocyte lineage. Functional assays will be performed by measuring ion channel activity. Maturation of differentiating cells toward a functional cardiac engineered tissue will be performed by biomechanical loading of cultures in with 3D peptide hydrogels. Verification of true cardiac phenotype will be investigated using mathematical modelling of ion channel function and functional regeneration confirmed using an in vivo experimental mouse model.

The project brings together a multi-disciplinary team of supervisors with expertise in stem cell biology, tissue engineering, cell physiology and the interaction of stem cells with innovative biomaterials for application in regenerative medicines. The project will also be closely linked with NHS partners at Liverpool and Newcastle. The Department houses the newly awarded MRC-ARUK Centre for Integrated research into Musculoskeletal Ageing which is a collaboration with Newcastle University and the University of Sheffield. Training in stem cell biology and cell physiology techniques will be carried out in the Department of Musculoskeletal Biology, University of Liverpool and training in cardiomyocyte biology will be carried out in the Institute of Genetic Medicine, Newcastle University.

To apply: please send your CV and a covering letter to Dr Rachel Oldershaw, with a copy to

Availability

Open to students worldwide

Funding information

Self-funded project

The project is open to both home and overseas students, it is UNFUNDED and applicants are encouraged to contact the Principal Supervisor directly to discuss their application and the project.

Assistance will be given to applications who are applying to international funding schemes.

The successful applicant will be expected to provide the funding for registration, tuition fees, all their own living expenses and research costs (bench fees) of £15,000 per year to cover charges associated with purchasing laboratory consumables. Details of costs can be found on the University website.

Supervisors

References

• Rogers CM, Deehan DJ, Knuth CA, Rose FR, Shakesheff KM, Oldershaw RA (2014) Biocompatibility and enhanced osteogenic differentiation of human mesenchymal stem cells in response to surface engineered poly(d,l-lactic-co-glycolic acid) microparticles. Journal of Biomedical Materials and Research Part A 102, 3872-3882.
• Knuth CA, Clark ME, Meeson AP, Khan SK, Dowen DJ, Deehan DJ, Oldershaw RA (2013) Low oxygen tension is critical for the culture of human mesenchymal stem cells with strong osteogenic potential from haemarthrosis fluid. Stem Cell Reviews and Reports 9, 599-608.
• Alfakir M, Dawe N, Eyre R, Tyson-Capper A, Britton K, Robson SC, Meeson AP. (2012) The temporal and spatial expression pattern of ABCG2 in the embryonic/fetal human heart. International Journal of Cardiology 156, 133-138.
• Feetham CH, Nunn N, Lewis R, Dart C. Barrett-Jolley R. (2015) TRPV4 and K(Ca) ion channels functionally couple as osmosensors in the paraventricular nucleus. Br J Pharmacol. 172;7:1753-1768. 

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