Module 8: Stem Cell Derived Cardiomyocytes: Tools for Investigating Cardiac Disease

 Module Leaders Dr David Elliott
Host Organisations
 Monash Immunology and Stem Cell Laboratories (MISCL), Monash University

Module description

Cardiac cells generated from differentiated human embryonic stem cells (hESCs) represent a potentially inexhaustible source of material for basic medical research and pharmaceutical development. However, a key limitation is the production in sufficient quantity of cells for use in both drug discovery platforms and in myocardial replacement therapy (MRT). This module aims to generate tools that will facilitate the large scale production of purified populations of human heart cells from the in vitro differentiation of HESCs. In turn, this will provide a platform for the development of model systems to investigate the molecular pathogenesis of cardiac disease. In the longer term, reagents and protocols established during the course of this study may enable the development of high throughput screens for novel compounds that target the molecular cascades underlying myocardial disease.



Above footage: Human embryonic stem cells can be used to produce functional heart cells for use in therapies or to develop new drugs for heart disease. This laboratory have tagged the cardiac muscle cells with a green fluorescent protein, which they can use to track and isolate human cardiac cells.This movie shows beating heart cells grown and cultured in the laboratory from embryonic stem cells filmed in normal light and then under UV light to image cells containing the green fluorescent protein.

Module Leader biographies

Dr David Elliott completed a PhD at the Victor Chang Cardiac Research Institute & the Walter and Eliza Hall Institute on the molecular control of heart development.  After his post-doctoral studies at Cambridge University he returned to MISCL to study human heart development using human embryonic stem cell derived cardiac cells as a model system.

Contact details

 Dr David Elliott        
 E-mail  david.elliott@med.monash.edu.au
 Phone  +61 3 9905 0676
 Web  www.med.monash.edu.au/miscl/

Selected publications

  1. Elliott, D.A., Kirk E., Chandra S., Yeoh, T. McKenzie F., Feneley M. and Harvey R.P. (2003). Cardiac homeobox gene NKX2.5 mutations and congenital heart disease: associations with Atrial Septal Defect and Hypoplastic Left Heart Syndrome. J. Am. Coll. Cardiol. 41: 2072-76.
  2. Elliott DA, Solloway MJ, Wise N, Biben C, Costa MW, Furtado MB, Lange M, Dunwoodie S, Harvey RP. (2006). A tyrosine-rich domain within homeodomain transcription factor Nkx2-5 is an essential element in the early cardiac transcriptional regulatory machinery. Development. 133: 1311-22.
  3. Elliott, D. A. and Harvey, R. P. (2007). Time to mend a broken heart. Stem Cell Research 1, 4-6..
  4. Schlaich MP, Parnell MM, Ahlers BA, Finch S, Marshall T, Zhang WZ, Kaye DM. (2004) Impaired Larginine transport and endothelial function in hypertensive and genetically predisposed normotensive subjects. Circulation; 110:3680-3686.
  5. Venardos, K. M., Zatta, A. J., Marshall, T., Ritchie, R. and Kaye, D. M. (2009). Reduced L-arginine transport contributes to the pathogenesis of myocardial ischemia-reperfusion injury. Journal of Cell. Biochem. [epub ahead of print}.
  6. Kaye DM, Hoshijima M, Chien KR. (2008). Reversing advanced heart failure by targeting Ca2+ cycling. Ann Rev Med 59: 13-28.
  7. Lang, R.J., Haynes, J.M., Kelly, J., Johnson, J., Mulholland, E.M, Baker L., Munsie, M. & Pouton.C.W. (2004). Electrical and neurotransmitter activity of mature neurons derived from mouse embryonic stem cells by sox-1 lineage selection and directed differentiation. Eur. J Neurosci. 20:3209-3221.
  8. Raye, WS, Tochon-Danguy, N, Pouton, CW and Haynes, JM. (2007)  Heterogeneous population of dopaminergic neurons derived from mouse embryonic stem cells: preliminary phenotyping based on receptor expression and function.  Eur J Neurosci., 25: 1961-1970.
  9. Pouton, C W and Haynes, J M (2007) Embryonic stem cells as a source of models for drug discovery.  Nature Rev. Drug  Discovery, 6: 605-616.  
  10. Khaira, S.K., Pouton C.W. & Haynes, J.M.. (2009).  P2X2, P2X4 and P2Y1 receptors elevate intracellular Ca2+ in mouse embryonic stem cell derived GABAergic neurons. Brit J Pharmacol., in press.