research Cris dos Remedios Director, Sydney Heart Bank University - - PowerPoint PPT Presentation
research Cris dos Remedios Director, Sydney Heart Bank University - - PowerPoint PPT Presentation
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
HERE IS THE PROBLEM
ANIMAL MODEL
- f HUMAN
HEART DISEASE Genetically uniform, Controlled food No stress TESTING, ON HUMAN Do Drugs Work Influence of a fatty diet? SPECIFIC PROTEIN CHANGES SPECIFIC GENE DEFECTS POST-TRANSLATIONAL MODIFICATION CARDIOMYOCYTE EXPERIMENTS RELAXATION- CONTRACTION
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
ANIMAL MODEL
- f HUMAN
HEART DISEASE Genetic CLONES, Controlled FOOD No STRESS DIRECT TESTING, ON HUMAN HEART MUSCLE CELLS IN CULTURE SPECIFIC PROTEIN CHANGES SPECIFIC GENE DEFECTS POST-TRANSLATIONAL MODIFICATION CARDIOMYOCYTE EXPERIMENTS DEFECTS in RELAXATION- CONTRACTION
X
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
- btained 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
USA PD Allen, B Kuhn, W Pu (Harvard) A Murphy, Jenny Van Eyk, Ray Winslow, (Johns Hopkins U), Meredith Bond, Katia Kontrogianni (Univ Maryland), Jill Tardiff , S Harris, H Granzier (U. Arizona), Tom Burghardt, M Ackerman (Mayo Clinic), K Campbell (U Kentucky), Pepe Gomez (U Virginia), S Sadayappan (Loyola U Chicago), Bob Horowitz (NIH,Bethesda), J Hall, D Thomas (U Minnesota) C Moravec (Cleveland Clin), D Warshaw (U Vermont) EUROPE N Hamdani, W. Linke (Bochum) T Kraft (Hannover) , T Steenman (Nantes) G Stienen, J Van der J Velden, W Simonides, S Rain, E Eringa, F De Man, D Dooijes, D Kuster, C Bezzina P Wijnkner (VU Med Ctr, Amsterdam)
- J. Soni (U Utrecht)
S Marston, M Schneider S Harding (Imperial London), J Kentish, E Ehler, P Bennett, P Elliott (King’s College London), A de Souza, ( P Riley (Univ Coll London), M Dunn (Dublin), J Frisén, J Odeberg, R Knoell (Karolinska), F Ponten (U Uppsala). ASIA- PACIFIC S Ishiwata (Waseda U) N Fukuda (Jikei U) K Yasuda, A Kimura (Tokyo Med), M Ferenczi , W Wang (NTU, Singapore) C dos Remedios, R Stocker, B Freedman, KY Ju, D Winlaw, B Hambly, M Kekic, P Bannon. J Chong (U Syd), B Herbert (Macquarie U), D Saint (U Adelaide), D Kaye, S Pepe (Baker IDI), A Keogh, P Macdonald (St Vincent’s Hosp), D Laver (U Newcastle), E Porrello, W Thomas (U Qld) J Ho (VCCRI), S Mihalidou (U Syd), G Ravenscroft (UWA);
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 2010 2011 2013 2014 2007 2006
ARE ANIMAL-FREE STRATEGIES SUCCESSFUL?
The Sydney Heart Bank SCIENTIFIC OUTPUT
50 100 150 200 250 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 Citations Year Series1
- 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
Animal + human Human only
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
5 10 15 20 25
9 11 13 15 23 14 6
Number of Hearts 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