Sydney Heart Bank A biobanking facility that provides an alternative to animal in research Cris dos Remedios Director, Sydney Heart Bank University of Sydney
HERE IS THE PROBLEM SPECIFIC PROTEIN CHANGES SPECIFIC GENE DEFECTS POST-TRANSLATIONAL MODIFICATION ANIMAL MODEL CARDIOMYOCYTE of HUMAN EXPERIMENTS HEART DISEASE TESTING, ON HUMAN Genetically Do Drugs Work RELAXATION- uniform, Influence of a fatty diet? CONTRACTION Controlled food No stress
WHAT IS WRONG WITH ANIMAL MODELS? • MOUSE HEART BEAT 800 BPM • CORONARY CIRCULATION IS DIFFERENT • DIFFERENT DRUG SENSITIVITIES • MOUSE MODELS DO NOT REFLECT DRUG METABOLISM • MOUSE MODELS OF CORONARY DISEASE ARE TOO SIMPLISTIC
HERE IS A SOLUTION SPECIFIC PROTEIN CHANGES X SPECIFIC GENE DEFECTS POST-TRANSLATIONAL MODIFICATION ANIMAL MODEL CARDIOMYOCYTE of HUMAN EXPERIMENTS HEART DISEASE DIRECT TESTING, ON Genetic CLONES, HUMAN HEART MUSCLE DEFECTS in Controlled FOOD CELLS IN CULTURE RELAXATION- No STRESS CONTRACTION
But … how can we test of human hearts? Isn’t this ethically impossible
• The Sydney Heart Bank contains over 16,000 tissue samples from more than 650 human hearts. • 400 heart are in heart failure and were obtained from the St Vincent’s Hospital Heart Transplant Unit. • >100 hearts are from organ donors where the heart was not able to be transplanted into patients with end-stage heart failure
ASIA- PACIFIC USA EUROPE S Ishiwata ( Waseda U ) PD Allen, B Kuhn, N Hamdani, W. Linke N Fukuda ( Jikei U ) W Pu ( Harvard ) ( Bochum ) K Yasuda, A Kimura ( Tokyo A Murphy, Jenny Van T Kraft ( Hannover ) , T Med ), M Ferenczi , W Wang Eyk, Ray Winslow, Steenman ( Nantes ) ( NTU, Singapore ) ( Johns Hopkins U ), G Stienen, J Van der J C dos Remedios, R Stocker, Meredith Bond, Katia Velden, W Simonides, S B Freedman, KY Ju, D Winlaw, Kontrogianni ( Univ Rain, E Eringa, F De Man, D B Hambly, M Kekic, P Bannon. Maryland ), Dooijes, D Kuster, C J Chong ( U Syd ), B Herbert Jill Tardiff , S Harris, H Bezzina P Wijnkner ( Macquarie U), D Saint ( U Granzier ( U. Arizona ), (VU Med Ctr, Amsterdam ) Adelaide ), D Kaye, S Pepe Tom Burghardt, M J. Soni ( U Utrecht ) ( Baker IDI ), A Keogh, P Ackerman ( Mayo S Marston, M Schneider S Macdonald ( St Vincent’s Clinic ), K Campbell ( U Harding ( Imperial London ), J Hosp ), D Laver ( U Newcastle ), Kentucky ), Pepe Kentish, E Ehler, P Bennett, E Porrello, W Thomas ( U Qld ) Gomez ( U Virginia ), S P Elliott ( King’s College J Ho ( VCCRI ), S Mihalidou (U Sadayappan ( Loyola U London ), A de Souza, ( Syd), G Ravenscroft Chicago), Bob Horowitz P Riley ( Univ Coll London ), M ( UWA ); ( NIH,Bethesda ), J Hall, Dunn ( Dublin ), J Frisén, J D Thomas ( U Minnesota ) Odeberg, R Knoell C Moravec (Cleveland Clin ), ( Karolinska ), F Ponten ( U D Warshaw ( U Vermont ) Uppsala ).
1991-2015: Sydney Heart Bank GLOBAL Active Collaborators
RESEARCH STRATEGIES
DOES THIS REDUCE ANIMAL EXPERIMENTATION ?
Scientists have to be convinced one-by-one to give up animals and use SHB human heart tissue. Data from a collaboration with Dr Jolanda van der Velden 2008 2009 2011 2013 2006 2007 2010 2014 �
ARE ANIMAL-FREE STRATEGIES SUCCESSFUL?
The Sydney Heart Bank SCIENTIFIC OUTPUT 250 200 150 Citations Series1 100 50 0 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 Year
Animal + human Human only • Number of SHB papers published using animas Plot of the number of scientific papers published by the SHB per year using ( RED ) only human tissue, and ( BLUE ) both animal experiments and human tissue
Human Heart Tissue Microarrays The first stage in the process One tissue section can test 60 heart samples in duplicate
• How do we know that changes in failing heart are not also found in healthy hearts?
91 SHB Healthy Donor Hearts 23 25 20 Number of Hearts 15 14 13 15 11 9 10 6 5 0 Age Group (years)
How the Sydney Heart Bank Works
Thank you to … • We thank Medical Advances Without Animals for their generous financial support for the purchase of a nitrogen vapour storage facility. • I am very grateful to the many students and post-doc that have assisted in the collection of the hearts in the Sydney Heart Bank
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