Heart Valve Tissue Engineering

Professor Sir Magdi Yacoub and Dr Adrian Chester - Heads of Group

Development of tissue engineering heart valve offers the potential for surgical replacement of diseased aortic valve with a ‘living’ valve that resembles the shape and function of the native valve.

Currently available heart valve substitutes have limitations and lack the subtle sophistication of the native valve, which may only be reproduced by a valve containing viable cells. Essential steps in this proposal of manufacturing a tissue engineered valve are the establishment of an optimal scaffold with inherent biological signals and mechanical properties, and the use of mechanical stimulation in a prescribed manner to stimulate the cellular components to adapt and adopt the desired phenotype and function. The group is based at the Harefield Heart Science Centre

The focus of our investigations are as follows:

• Understanding the function of heart valves at the cellular and molecular level
• Mechanisms that mediate aortic stenosis and mitral valve disease
• Phenotypic and functional characterisation of stem cells suitable for use in heart valve tissue engineering
• Self assembly scaffold technology
• Decoration of synthetic materials to make intelligent  scaffolds
• Mechanical and biological conditioning of heart valve constructs
• Development of strategies to prevent calcification of tissue engineered valves   

Selected Publications

 M.H. Yacoub, J.J. Takkenberg. Will heart valve tissue engineering change the world? Nat Clin Pract Cardiovasc Med. 2005;2:60-1.

L. Osman, A. H. Chester, M. Amrani, M. H. Yacoub, and R. T. Smolenski. A novel role of extracellular nucleotides in valve calcification: a potential target for atorvastatin. Circulation 2006;114 (1 Suppl):I566-I572.

L. Osman, M. H. Yacoub, N. Latif, M. Amrani, and A. H. Chester. Role of human valve interstitial cells in valve calcification and their response to atorvastatin. Circulation 2006;114 (1 Suppl):I547-I552.

N. Latif, P. Sarathchandra, P. S. Thomas, J. Antoniw, P. Batten, A. H. Chester, P. M. Taylor, and M. H. Yacoub. Characterization of structural and signaling molecules by human valve interstitial cells and comparison to human mesenchymal stem cells. J.Heart Valve Dis. 2007;16:56-66.

L. Osman, A.H. Chester, P. Sarathchandra, N. Latif, W. Meng, P.M. Taylor, M.H. Yacoub . A novel role of the sympatho-adrenergic system in regulating valve calcification. Circulation; 2007;116 (11 Suppl):I282-I287.

I. El-Hamamsy, K. Balachandran, M.H. Yacoub, L.M. Stevens, P. Sarathchandra, P.M. Taylor, A.P .Yoganathan, A.H. Chester. Endothelium-dependent regulation of the mechanical properties of aortic valve cusps. J Am Coll Cardiol.  , 2009;53:1448-1455.

F. Colazzo, A.H. Chester, P.M. Taylor, M.H. Yacoub. Induction of mesenchymal to endothelial transformation of adipose-derived stem cells. J Heart Valve Dis. 2010 ;19:736-744.

I. El-Hamamsy, Z. Eryigit, L.M. Stevens, Z. Sarang, R. George, L. Clark, G. Melina, J.J. Takkenberg, M.H. Yacoub. Long-term outcomes after autograft versus homograft aortic root replacement in adults with aortic valve disease: a randomised controlled trial. Lancet. 2010;376:524-531.

F.  Colazzo, P. Sarathchandra, R.T. Smolenski, A.H. Chester, Y.T. Tseng, J.T. Czernuszka, M.H. Yacoub, P.M. Taylor. Extracellular matrix production by adipose-derived stem cells: implications for heart valve tissue engineering. Biomaterials. 2011;32:119-127.

N. Krishnamoorthy, M.H. Yacoub, S.N. Yaliraki. A computational modeling approach for enhancing self-assembly and biofunctionalisation of collagen biomimetic peptides. Biomaterials. 2011;32:7275-7285.