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Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
Stem Cells - Biology ppt slides
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Stem Cells - Biology ppt slides

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  • Interaction between NO and superoxide appears to be an important feature of vascular disease models. However, its importance in human atherosclerosis is unclear.
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    • 1. Stem Cells Keith Channon Department of Cardiovascular Medicine University of Oxford John Radcliffe Hospital, Oxford For more slides click here DOWNLOAD THIS SLIDE
    • 2. Adult Stem Cells <ul><li>Unique cells that are capable of self-renewal </li></ul><ul><li>Have the ability to differentiate through a committed lineage </li></ul><ul><li>Undergo further development within an adult organism v embryo </li></ul><ul><li>They are multi(pluri)potent v totipotent </li></ul>
    • 3. Stem Cells
    • 4. N Engl J Med 2003;349:570-82. Phenotypically Characterised Adult Stem Cells
    • 5. Why are Stem Cells Relevant to Interventional Cardiology? Understanding stem cell biology challenges and informs our understanding of cardiovascular disease Stem cells may offer new therapeutic approaches in cardiovascular disease
    • 6. <ul><li>Multinucleate </li></ul><ul><li>Negative for </li></ul><ul><li>Connexin 43 </li></ul><ul><li>D esmosomes </li></ul><ul><li>C adherin </li></ul><ul><li>No integration </li></ul>Skeletal Myoblast Cell Transplant in Ischaemic Cardiomyopathy Menasché P et al. Myoblast transplantation for heart failure. Lancet 2001
    • 7. <ul><li>Lin - c- kit POS bone marrow cells from EGFP male mice to myocardium of female C57B6 mouse </li></ul><ul><li>Injected in peri-infarct tissue 3-5hrs after LAD ligation </li></ul>Nature 2001;410:701-705
    • 8. Red=Cardiac Myosin a Green=Cell Nuclei c-kit neg c-kit pos
    • 9. &nbsp;
    • 10. <ul><li>CD117+ CD90+ CD34– MSCs from BM male rats isolated by adhesion to polystyrene, purified by immunoselection, </li></ul><ul><li>Transfected with murine Akt by VSV retrovirus </li></ul><ul><li>Permanent CAL of LAD in female rats </li></ul><ul><li>60 mins post CAL MSCs injected 5 peri-infarct sites </li></ul>Nature Medicine 2003;9:1195-1201
    • 11. Engraftment does not occur in absence of MI……..
    • 12. &nbsp;
    • 13. &nbsp;
    • 14. &nbsp;
    • 15. Conclusions <ul><li>Bone marrow-derived lineage negative progenitors regenerate infarcted murine myocardium </li></ul><ul><li>Autologous “skeletal lineage” progenitors improve cardiac function and survive in infarction scar </li></ul>
    • 16. Bone Marrow Derived Stem Cells : Vascular Injury
    • 17. Bone Marrow Derived Stem Cells : Atherosclerosis
    • 18. Bone Marrow Derived Stem Cells : Transplant Vasculopathy
    • 19. Stem Cells in Human Restenosis ? smc-actin c-kit+ Hibbert et al. Am J Physiol 2004
    • 20. Stem Cells in Human Restenosis ? smc-actin c-kit+ Hibbert et al. Am J Physiol 2004
    • 21. <ul><li>Nude mice </li></ul><ul><li>1 day post femoral artery excision </li></ul><ul><li>Intracardiac medium, human µ vascular ECs or EPCs </li></ul>
    • 22. Endothelial Progenitor Cells- Role in Endothelial Maintenance Jonathan Hill, 2004 high blood pressure high cholesterol / triglycerides smoking diabetes infections other RISK FACTORS Cytokines e.g. G-CSF STATINS EXERCISE
    • 23. J. Hill et al. NEJM 2003; 348:593-600
    • 24. &nbsp;
    • 25. &nbsp;
    • 26. Mean ~ CK 800 U/L
    • 27. &nbsp;
    • 28. TOPCARE-AMI: Late MRI follow up
    • 29. TOPCARE-AMI: Late MRI follow up
    • 30. The STIMULATE Trial <ul><li>Title Multicenter, randomized controlled study of transplantation of bone marrow-derived progenitor cells into infarct vessels of patients following an acute myocardial infarction, acutely re-vascularised by percutaneous intervention. </li></ul><ul><li>Principal Investigators Prof. Dr. A. M. Zeiher &amp; J.W. Goethe, University of Frankfurt </li></ul><ul><li>Sponsor Cardio-Cell, Zutphen, the Netherlands (parent Cryo Cell using subsid MainGen in Frankfurt ) </li></ul><ul><li>Monitoring CorTrial, Berlin </li></ul><ul><li>Objective To assess the safety and efficacy of intracoronary therapy with bone marrow-derived autologous progenitor cells with respect to improvement of myocardial function after an acute myocardial infarction treated by PTCA. </li></ul><ul><li>Design Multi-center,Randomized 1:1 </li></ul><ul><li>Primary endpoint improvement of left ventricular dysfunction at rest and during Dobutamine stress, assessed by echocardiography at 4 months. </li></ul>
    • 31. THE PRIMATIVE Trial Leicester <ul><li>P ercutaneous R andomised I nfusion of M arrow A spirate T o I mprove V entricular E fficiency </li></ul><ul><li>Principal Investigators Tony Gershlick, Nilesh Samani et al. </li></ul><ul><li>Objective Assess the safety and efficacy of intracoronary therapy with bone marrow-derived autologous progenitor cells delivered at salvage PCI (DES) after acute MI, either early or late. </li></ul><ul><li>Design Single-center, Randomized, Placebo-Controlled n=150 </li></ul><ul><li>Primary endpoint improvement of left ventricular function, assessed by echocardiography and cardiac MRI at 4 months, and clinical events, up to 5 years. </li></ul>
    • 32. Saline GM-CSF Saline GM-CSF
    • 33. &nbsp;
    • 34. EPC Colony-Forming Capacity Following G-CSF J. Hill et al. JACC 2005; in press
    • 35. G-CSF and In-stent Restenosis after MI Kang et al. Lancet 2004 <ul><li>Patients undergoing PCI with stenting of culprit artery following MI (3 days to 9 months) randomized to G-CSF ± apheresis / IC infusion, control </li></ul><ul><li>No AE’s associated with G-CSF treatment </li></ul><ul><li>At 6 month F/U, improved treadmill time, LVEF, SPECT perfusion in cell infusion group </li></ul><ul><li>In-stent restenosis determined in 7/10 G-CSF treated patients, 0/1 control </li></ul><ul><li>Study terminated </li></ul>
    • 36. Shirota et al. Biomaterials 2003 vWF Flk-1 LDL-Uptake Isolation of EPCs for Stent Delivery
    • 37. &nbsp;
    • 38. &nbsp;
    • 39. Stem Cells in Interventional Cardiology vascular disease risk, biology, drug therapy cell therapy for post-MI repair cell therapy in PCI
    • 40. Future Directions <ul><li>Circulating or Bone Marrow Progenitor Cells? </li></ul><ul><ul><li>Harvest or not, which subset? </li></ul></ul><ul><ul><li>Statins </li></ul></ul><ul><ul><li>Cytokine stimulation to release- e.g. CXCR4, new drugs </li></ul></ul><ul><li>Circulating / Bone Marrow progenitor cells clinical trials- need to be blinded, placebo controlled, with hard end points </li></ul><ul><li>Understanding mechanisms remains critical to evaluating and targeting real benefits </li></ul>

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