1. Cell Therapy in CV Disease: Future Directions

2. 2 Anversa P, Nadal-Ginard B et al. Nature. 2002;415:240-3. Cardiac renewal: Is the goal in sight? “Remaining young at heart is a desirable but elusive goal. Myocyte regeneration may accomplish just that. Continuous cell renewal in adult myocardium was thought to be impossible; multipotent stem cells may be able to renew myocardium and, under certain circumstances, can be coaxed to repair the broken heart after infarction.”

3. 3 Stem cell therapy: More questions than answers? Routes of delivery Surgical vs percutaneous Cell type and marker Myoblast vs BM CD 34/ AC133/ SP Timing of delivery Acute vs chronic Target patient population Best criteria Cell origin Embryonic vs adult BM vs peripheral Culture expanded vs fresh Courtesy of Timothy Henry, MD. ? Dose Dose response

4. 4 CCTRN: Addressing gaps in the knowledge base NHLBI Cardiovascular Cell Therapy Research Network, established January 2007 Nat Clin Pract Cardiovasc Med. 2007;4:403. DCC = Data Coordinating Center MHI = Minneapolis Heart Institute Network DCC University of Texas Network DCC University of Texas Universit y of Florida Vanderbil t Universit y Cleveland Clinic MHI U of Minn Texas Heart Institute

5. 5 CCTRN: Goal and initial phase I/II clinical trials Nat Clin Pract Cardiovasc Med. 2007;4:403. Goal: Accelerate research into use of cell-based therapies in management of CV diseases TIME Effect of timing of post-MI BMC administration on measures of LV function Late TIME Effect of late (2-3 weeks) post-MI BMC administration on measures of LV function FOCUS Effect of transmyocardial BMC administration on measures of LV function in patients with chronic IHD

6. 6 Year 02Year 01Year 03Year 05 PRC DSMB Review Protocol 1 Development Protocol 1 Protocol 2 Development PRC DSMB Review Protocol 2 Protocol 3 Development Protocol 3 PRC DSMB Review Courtesy Timothy Henry, MD. CCTRN: Timeline of trials Year 04

7. 7 Summary Current clinical efforts have focused in three overlapping areas: –Repair of myocardium after MI –Reconstitution of myocardium in setting of chronic HF –Therapeutic angiogenesis Promising early clinical experience with BMC, endothelial cells, and skeletal myoblasts Numerous questions regarding techniques and mechanism of benefit remain –Ongoing trials by the NHLBI CCTRN and other research groups should provide insight