Presentation on theme: "Department of Cardiovascular Medicine John Radcliffe Hospital, Oxford"— Presentation transcript:
1 Department of Cardiovascular Medicine John Radcliffe Hospital, Oxford Stem CellsInteraction between NO and superoxide appears to be an important feature of vascular disease models. However, its importance in human atherosclerosis is unclear.Keith ChannonDepartment of Cardiovascular MedicineUniversity of OxfordJohn Radcliffe Hospital, Oxford
2 Adult Stem Cells Unique cells that are capable of self-renewal Have the ability to differentiate through a committed lineageUndergo further development within an adult organism v embryoThey are multi(pluri)potent v totipotent
4 Phenotypically Characterised Adult Stem Cells N Engl J Med 2003;349:
5 Why are Stem Cells Relevant to Interventional Cardiology? Stem cells may offer new therapeutic approaches in cardiovascular diseaseUnderstanding stem cell biology challenges and informs our understanding of cardiovascular disease
6 Skeletal Myoblast Cell Transplant in Ischaemic Cardiomyopathy MultinucleateNegative forConnexin 43DesmosomesCadherinNo integrationMenasché P et al. Myoblast transplantation for heart failure. Lancet 2001
7 Injected in peri-infarct tissue 3-5hrs after LAD ligation Nature 2001;410:Lin- c-kitPOS bone marrow cells from EGFP male mice to myocardium of female C57B6mouseInjected in peri-infarct tissue 3-5hrs after LAD ligation
10 Transfected with murine Akt by VSV retrovirus Nature Medicine 2003;9:CD117+ CD90+ CD34– MSCs from BM male rats isolated by adhesion to polystyrene, purified by immunoselection,Transfected with murine Akt by VSV retrovirusPermanent CAL of LAD in female rats60 mins post CAL MSCs injected 5 peri-infarct sites
11 Engraftment does not occur in absence of MI……..
30 The STIMULATE TrialTitle 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.Principal Investigators Prof. Dr. A. M. Zeiher & J.W. Goethe, University of FrankfurtSponsor Cardio-Cell, Zutphen, the Netherlands (parent Cryo Cell using subsid MainGen in Frankfurt )Monitoring CorTrial, BerlinObjective 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.Design Multi-center,Randomized 1:1Primary endpoint improvement of left ventricular dysfunction at rest and during Dobutamine stress, assessed by echocardiography at 4 months.
31 THE PRIMATIVE Trial Leicester Percutaneous Randomised Infusion of Marrow Aspirate To Improve Ventricular EfficiencyPrincipal Investigators Tony Gershlick, Nilesh Samani et al.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.Design Single-center, Randomized, Placebo-Controlled n=150Primary endpoint improvement of left ventricular function, assessed by echocardiography and cardiac MRI at 4 months, and clinical events, up to 5 years.
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 Patients undergoing PCI with stenting of culprit artery following MI (3 days to 9 months) randomized to G-CSF ± apheresis / IC infusion, controlNo AE’s associated with G-CSF treatmentAt 6 month F/U, improved treadmill time, LVEF, SPECT perfusion in cell infusion groupIn-stent restenosis determined in 7/10 G-CSF treated patients, 0/1 controlStudy terminated
36 Isolation of EPCs for Stent Delivery vWFFlk-1LDL-UptakeShirota et al. Biomaterials 2003
39 Stem Cells in Interventional Cardiology vascular disease risk, biology, drug therapycell therapy for post-MI repaircell therapy in PCI
40 Future Directions Circulating or Bone Marrow Progenitor Cells? Harvest or not, which subset?StatinsCytokine stimulation to release- e.g. CXCR4, new drugsCirculating / Bone Marrow progenitor cells clinical trials- need to be blinded, placebo controlled, with hard end pointsUnderstanding mechanisms remains critical to evaluating and targeting real benefits