Investigating the therapeutic efficacy of resident cardiac stem cells

About the Project

The studentship aims to characterise human cardiac resident stem cells and their potential for effecting functional cardiac repair.

Stem cells of both bone marrow and cardiac origin have been used clinically to affect cardiac repair but with limited success. Improved treatments require methods for maturing differentiating cells toward functional cardiomyocytes and engineering into cardiac-like tissue.

We have characterised a novel human cardiac stem cell population that is phenotypically comparable to mesenchymal stem cells (MSCs), exhibiting CFU-F formation, expression of key cell surface antigens and paracrine activity. Furthermore, they can differentiate toward cardiomyocyte cell lineage, displaying striation formation essential for cardiomyocyte function.

Aims:

1. i) Generation of functional cardiac tissue
   Cardiac stem cells will be differentiated to cardiomyocytes and phenotyped by quantitative gene/ protein expression analyses to determine maturation status. Action potential generation, Ca2+ activated-Ca2+ release and myocyte contractility will be measured by multi-electrode array.
   
   (b) Metabolic profiling of stem cell differentiation to cardiomyocyte cell lineage
   Characterisation and expansion of understanding of the metabolic pathways involved during the differentiation cardiac-derived stem cells will be used to refine existing culture methodologies. The student will investigate intracellular and secreted metabolites using a combination of NMR metabolomics and MS techniques to address critical questions regarding the suitability native cardiac tissue-derived stem cells for translational applications.

The project will include a multidisciplinary approach with training provided in the maintenance and differentiation of induced pluripotent stem cells to cardiomyocytes, and their characterisation using molecular biology techniques to measure gene (quantitative PCR) and protein expression (ELISA), immunocytochemistry and Western blotting. Metabolic function of the cells will be measured in response to inflammatory mediators using multi-omics techniques that include transcriptomics and metabolomics (NMR and mass spectrometry) with real-time bioenergetic measurements made by Seahorse analyser.

Email CV and cover letter to Dr Rachel Oldershaw, Rachel.oldershaw@liverpool.ac.uk

Funding Notes

The research cost associated with the project is £15000 per annum for the purchase of laboratory reagents, including molecular biology and biochemical reagents, the use of shared research facilities for multi-omics analyses and licences for software used in bioinformatics.