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Stem Cell Therapy & CV Innovations Madrid, April 23 - 24, 2009

Stem Cell Therapy & CV Innovations Madrid, April 23 - 24, 2009. Next Steps in Heart Replacement My Clinical View William Wijns Cardiovascular Center, Aalst (B). Next Steps in Heart Replacement. My fundamental view My preclinical view My translational view My clinical view My global view.

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Stem Cell Therapy & CV Innovations Madrid, April 23 - 24, 2009

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  1. Stem Cell Therapy & CV InnovationsMadrid, April 23 - 24, 2009 Next Steps in Heart Replacement My Clinical View William Wijns Cardiovascular Center, Aalst (B) www.europcronline.com/

  2. Next Steps in Heart Replacement • My fundamental view • My preclinical view • My translational view • My clinical view • My global view What are the unmet needs ? Stem Cell Therapy and CV Innovations # 6: Closing Session

  3. Clinical Needs for CV Cell TherapyMany Factors to be Considered • PATIENT • Disease • Risk Profile • Bone Marrow • CELL PRODUCT • Type • Source and harvest • Function and number STEM CELL THERAPY • END-POINTS and • “MECHANISMS AT WORK” • Target organ – heart • Remote Homing • Arrhythmias • Coronary vasculature CELL PROCESSING CELL DELIVERY From J. Bartunek et al

  4. Next Steps in Heart Replacement • My clinical view • My fundamental view • My preclinical view • My translational view • My global view

  5. Clinical Needs for CV Cell Therapy • (First) Acute Myocardial Infarction • Chronic Ischemic Heart Failure • End-stage Heart Disease • Non-revascularisable Patient • Non Ischemic Cardiomyopathy • Endothelial dysfunction • Arrhythmias & Conduction defects • A A A and aortic disease • . . . / . . .

  6. Vascularization  Apoptosis  • Bone marrrow cells or circulating progenitor cells • Improve neovascularization • Differentiate to cardiac myocytes (?) • Release paracrine factors • Influence LV remodeling Paracrine factors LV- Dilatation Cardiac Regeneration Function of Stem/Progenitor Cells in AMI Acute Infarction  Adapted from A. Zeiher et al

  7. Clinical Trials with Adult Hematopoietic Stem Cells Only bad cases may benefit (ejection fraction < 40 %) Overall modest efficacy but clinical safety demonstrated over 1 to 2 years period Abdel-Latif, Arch Intern Med 2007

  8. STEMI reperfusion treatment in Europe STENT for LIFE

  9. Nationwide „thrombolytic strategy“ for STEMI results in 46% untreated patients ! % from all STEMI STENT for LIFE

  10. Reperfusion strategy paradox • Most people think that thrombolysis is a kind oftreatment widely available for patientseverywhere, while p-PCI is limited in its availability • The opposite is true: far more patients receive reperfusion treatment in countries with low use of thrombolysis and high use of p-PCI ! STENT for LIFE

  11. In-hospital mortality of all STEMI pts in countries with p-PCI dominance vs countries with thrombolysis dominance % STENT for LIFE

  12. Clinical Needs for CV Cell Therapy ? • (First) Acute Myocardial Infarction • Chronic Ischemic Heart Failure • End-stage Heart Disease • Non-revascularisable Patient • Non Ischemic Cardiomyopathy • Endothelial dysfunction • Arrhythmias & Conduction defects • A A A and aortic disease • . . . / . . .

  13. Mortality of Acute CAD decreases, Heart Failure population increases Balloon angio1977 Stenting1987 StreptokinaseGISSI 1, 1986 tPAGUSTO-I, 1995 MORTALITY Time

  14. A true challengeCardiovascular disease in Europe

  15. Functionality vs Lack of Proper Signalling Damaged adult heart is devoid of embryonic signalling and may fail to recapitulate necessary milieu to stimulate myocardial specification resulting in limited functionality and unwanted signalling/differentiation Olson, Nat Medicine 2004; Chien, Nature 2004;Wang, J Thorac Cardiovasc Surg 2001; Yoon, Circulation 2004; Befhar, JMCC 2007 From J Bartunek

  16. Clinical Needs for CV Cell Therapy ? +++ • (First) Acute Myocardial Infarction • Chronic Ischemic Heart Failure • End-stage Heart Disease • Non-revascularisable Patient • Non Ischemic Cardiomyopathy • Endothelial dysfunction • Arrhythmias & Conduction defects • A A A and aortic disease • . . . / . . .

  17. Clinical Needs for CV Cell Therapy • End-stage Heart Disease New hearts for old and new needs Cardiac replacement Bridge? Destination? Both? Artificial hearts and biosensors Xenotransplant

  18. Current treatments are palliative only and costly * cost /year of life and /patient (US $) American College of Cardiology / American Heart Association

  19. Clinical Needs for CV Cell Therapy ? +++ + • (First) Acute Myocardial Infarction • Chronic Ischemic Heart Failure • End-stage Heart Disease • Non-revascularisable Patient • Non Ischemic Cardiomyopathy • Endothelial dysfunction • Arrhythmias & Conduction defects • A A A and aortic disease • . . . / . . .

  20. Abnormal Resistance in Mildly Atherosclerotic Coronary Arteries Conductance Arteries Resistance Arteries >500 µ <500 µ Microvasculature Pa 100 MACRO MICRO

  21. Clinical Needs for CV Cell Therapy ? +++ + ▼ • (First) Acute Myocardial Infarction • Chronic Ischemic Heart Failure • End-stage Heart Disease • Non-revascularisable Patient (PVD?) • Non Ischemic Cardiomyopathy • Endothelial dysfunction • Arrhythmias & Conduction defects • A A A and aortic disease • . . . / . . .

  22. Clinical Needs for CV Cell Therapy ? +++ + ▼ ? • (First) Acute Myocardial Infarction • Chronic Ischemic Heart Failure • End-stage Heart Disease • Non-revascularisable Patient • Non Ischemic Cardiomyopathy • Endothelial dysfunction • Arrhythmias & Conduction defects • A A A and aortic disease • . . . / . . .

  23. Circulation 2000;101:1899-1906 Prognostic Impact of Coronary Vasodilator Dysfunction on Adverse Long-Term Outcome of Coronary Heart Disease Volker Schächinger, MD; Martina B. Britten, MD; Andreas M. Zeiher, MD From the Department of Internal Medicine IV, Division of Cardiology, J.W. Goethe University, Frankfurt, Germany

  24. CVD in Europe 2006Ageing of the Population Euro Heart Survey ESC

  25. Clinical Needs for CV Cell Therapy ? +++ + ▼ ? ++ • (First) Acute Myocardial Infarction • Chronic Ischemic Heart Failure • End-stage Heart Disease • Non-revascularisable Patient • Non Ischemic Cardiomyopathy • Endothelial dysfunction • Arrhythmias & Conduction defects • A A A and aortic disease • . . . / . . .

  26. Clinical Needs for CV Cell Therapy ? +++ ++ ▼ ? ++ ? • (First) Acute Myocardial Infarction • Chronic Ischemic Heart Failure • End-stage Heart Disease • Non-revascularisable Patient • Non Ischemic Cardiomyopathy • Endothelial dysfunction • Arrhythmias & Conduction defects • A A A and aortic disease • . . . / . . .

  27. Isolation of "side population" progenitor cells from healthy arteries of adult mice Sainz J, Al Haj Zen A, Caligiuri G, Demerens C, Urbain D, Lemitre M, Lafont A. Arterioscler Thromb Vasc Biol. 2006 Feb;26(2):281-6. Epub 2005 Nov 23. Gingival fibroblasts inhibit MMP-1 and MMP-3 activities in an ex-vivo artery model Naveau A, Reinald N, Fournier B, Durand E, Lafont A, Coulomb B, Gogly B. Connect Tissue Res. 2007;48(6):300-8.

  28. Clinical Needs for CV Cell Therapy ? +++ ++ ▼ ? ++ ? ▲ • (First) Acute Myocardial Infarction • Chronic Ischemic Heart Failure • End-stage Heart Disease • Non-revascularisable Patient • Non Ischemic Cardiomyopathy • Endothelial dysfunction • Arrhythmias & Conduction defects • A A A and aortic disease • . . . / . . .

  29. 5 million years 50 years

  30. CVD in Europe 2006Ageing of the Population

  31. Disease burden Courtesy P. Puska

  32. Next Steps in Heart Replacement • My fundamental view • My preclinical view • My translational view • My clinical view • My global view What are the solutions for the ever growing unmet needs ? Disruptive technologies Stem Cell Therapy and CV Innovations # 6: Closing Session

  33. Conflict of Interest for William Wijns I disclose the following financial relationships: Consulting Fees: on my behalf go to the Cardiovascular Research Center Aalst Contracted Research: between the Cardiovascular Research Center Aalst and several pharmaceutical and device companies Ownership Interest: Cardiovascular Research Center Aalst is co-founder of Cardio³BioSciences, a start-up company focusing on cell-based therapies www.europcronline.com/

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