1. IN THE NAME OF GOD

3. What are Stem Cells? Stem cells are a class of undifferentiated cells that are able to differentiate into specialized cell types. Commonly, stem cells come from two main sources: 1. Embryos formed during the blastocyst phase of embryological development (embryonic stem cells) 2. Adult tissue (adult stem cells). Both types are generally characterized by their potency, or potential to differentiate into different cell types (such as skin, muscle, bone, etc.).

4. Cardiovascular disease treatment A team of researchers from Massachusetts General Hospital reported in PNAS Early Edition (July 2013 issue) that they were able to create blood vessels in laboratory mice using human stem cells The scientists extracted vascular precursor cells derived from human-induced pluripotent stem cells from one group of adults with type 1 diabetes as well as from another group of “healthy” adults. They were then implanted onto the surface of the brains of the mice. Within two weeks of implanting the stem cells, networks of blood-perfused vessels had been formed - they lasted for 280 days. These new blood vessels were as good as the adjacent natural ones. The authors explained that using stem cells to repair or regenerate blood vessels could eventually help treat human patients with cardiovascular and vascular diseases

5. Possible mechanisms for successful cardiac regenerative therapy. Possible mechanisms for successful cardiac regenerative therapy.

6. Methods of Stem Cell Delivery A major goal of cardiac stem cell therapy is to transplant enough cells into the myocardium at the site of injury or infarction to maximize restoration of function. Several different approaches currently are being used to deliver stem cells. Transvascular Route Direct Injection Into the Ventricular Wall Approach involves the delivery of cells through one of the cardiac veins directly into the myocardium

7. Validating intramyocardial bone marrow stem cell therapy in combination with coronary artery bypass grafting, the PERFECT Phase III randomized multicenter trial: study protocol for a randomized controlled trial For the last decade continuous efforts have been made to translate regenerative cell therapy The PERFECT trial has been designed as a prospective, randomized, double-blind, placebo controlled, multicenter trial, analyzing the effect of intramyocardial CD 133+ bone marrow stem cell injection in combination with coronary artery bypass grafting on postoperative left ventricular function

8. Patient inclusion criteria Coronary artery disease with indication for CABG and previous myocardial infarction LVEF less than 30% measured by cardiac MRI Akinetic/hypokinetic/hibernating left ventricular areas localized by cardiac stress MRI Absence of any moderate to severe valvular heart disease requiring concomitant valve replacement or reconstruction Age between 18 and 79 years

9. Exclusion criteria Exclusion criteria Emergency operation Acute myocardial infarction within last 2 weeks Resuscitation in combination with ventricular arrhythmias within the last 14 days before treatment Active cancer, organ transplantation, end- stage renal disorder Infection (CRP≥20 mg/L, temperature ≥38.5 °C) Contraindication for MRI

10. patients undergoing coronary artery bypass grafting in combination with intra- myocardial CD133+ cell injection will have a higher LV ejection fraction than patient who undergo CABG alone, measured 6 months after the operation.

11. Low EFGood ViabilityGood Run offCABG Low EFLow ViabilityGood Run off CABG+ preferably Stem- cells injection Low EFLow or NoViabilityBad or No Run off (Sever disease) Stem cells injection probably CABG

12. Conclusions Although at this time no data support either cell-based or specific stem cell therapies as standard clinical practice for cardiac applications, there is a wealth of preclinical and early clinical data showing safety, feasibility, and early efficacy of adult cell-based therapy. Adult stem cell therapies should therefore proceed into randomized, placebo-controlled, double-blind clinical trials. The ongoing rigorously designed trials will contribute greatly to this emerging and exciting new therapeutic approach for diseases of the cardiovascular system.

13. THANK YOU FOR YOUR ATTENTION