research Cris dos Remedios Director, Sydney Heart Bank University - - PowerPoint PPT Presentation

research
SMART_READER_LITE
LIVE PREVIEW

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


slide-1
SLIDE 1

Sydney Heart Bank A biobanking facility that provides an alternative to animal in research

Cris dos Remedios Director, Sydney Heart Bank University of Sydney

slide-2
SLIDE 2

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

slide-3
SLIDE 3

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

slide-4
SLIDE 4

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

slide-5
SLIDE 5

But … how can we test of human hearts? Isn’t this ethically impossible

slide-6
SLIDE 6
  • 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

slide-7
SLIDE 7

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);

slide-8
SLIDE 8

1991-2015: Sydney Heart Bank GLOBAL Active Collaborators

slide-9
SLIDE 9

RESEARCH STRATEGIES

slide-10
SLIDE 10

DOES THIS REDUCE ANIMAL EXPERIMENTATION?

slide-11
SLIDE 11

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

slide-12
SLIDE 12

ARE ANIMAL-FREE STRATEGIES SUCCESSFUL?

slide-13
SLIDE 13

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

slide-14
SLIDE 14
  • 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

slide-15
SLIDE 15

Human Heart Tissue Microarrays The first stage in the process

One tissue section can test 60 heart samples in duplicate

slide-16
SLIDE 16
  • How do we know that

changes in failing heart are not also found in healthy hearts?

slide-17
SLIDE 17
slide-18
SLIDE 18

91 SHB Healthy Donor Hearts

5 10 15 20 25

9 11 13 15 23 14 6

Number of Hearts Age Group (years)

slide-19
SLIDE 19

How the Sydney Heart Bank Works

slide-20
SLIDE 20

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