Skip to main content


NIH Symposium: Challenges & Promise of Cell-Based Therapies
May 6, 2008
Natcher Conference Center
NIH Main Campus, Bethesda, Maryland

Session 2: Cardiac Disorders

Moderator: Sonia Skarlatos, Ph.D.; National Heart, Lung, and Blood Institute, NIH

Clinical Trials of Cell-Based Therapies for Cardiac Repair
Douglas W. Losordo, M.D.; Northwestern University

Dr. Losordo observed that the literature features numerous reports of small, exploratory studies of cell-based therapies for cardiac repair. However, this discussion will highlight studies that enrolled at least twenty subjects. The Bone Marrow Transfer to Enhance ST-Elevation Infarct Regeneration (BOOST) Trial, which investigated the intracoronary transfer of bone marrow cells following myocardial infarction (MI) (Meyer GP, Circulation 2006;113:1272-1284), indicated a notable increase in the mean left ventricular ejection fraction (LVEF) after six months. At 18 months, however, some loss of this effect was observed. Similarly, a trial that explored the intracoronary transplantation of autologous bone marrow MSCs in patients with acute MI demonstrated a statistically significant improvement in LVEF (Chen SL, Am J Cardiol 2004;94:92-95). In the Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) trial, patients received an intracoronary infusion of bone marrow progenitor cells 3-6 days after successful acute reperfusion therapy for MI. At four months follow-up, the LVEF was greater in the treatment group (Schachinger V, N Engl J Med 2006;355:1210-1221). In another study, a population of patients who had undergone an event that chronically reduced LVEF received an infusion of their own bone marrow mononuclear cells, resulting in a moderate increase in ventricular function (Assmus B, N Engl J Med 2006;355:1222-1232). In the Autologous Stem cell Transplantation in Acute Myocardial Infarction (ASTAMI) trial (Lunde K, J Am Coll Cardiol 2008;51:674-676), which featured intracoronary injection of autologous bone marrow mononuclear cells following MI, there was no observed change in treatment versus control after 12 months. A study led by Janssens S, (Lancet 2006;367:113-121) also showed no difference between the control and BM stem cell-infused groups. Dr. Losordo noted that a key factor in assessing these trials is that they feature numerous procedural differences such as cell preparations and timing of infusion.

CD34+ cells have also been used in clinical studies of cell-based repair of myocardial injury. Injection of human CD34+ cells into rats with acute infarction has been shown to improve capillary density and myocardial function (Kocher AA, Nat Med 2001;7:430-436). A recent clinical trial has investigated whether CD34+ cells could improve function in patients with angina who were not candidates for surgical revascularization procedures (Losordo DW, Circulation 2007;115:3165-3172). Promising results led to Phase 2b of the study, which was recently completed (Menasche P, Circulation 2008;117:1189-1200). However, the injection of cultured myoblasts was associated with an increased number of postoperative arrhythmic events, suggesting that further investigation is needed.

In conclusion, Dr. Losordo noted that autologous cell administration via intracoronary and intramyocardial routes has not resulted in adverse safety signals. However, intramyocardial injection of skeletal myoblasts has been associated with an increased incidence of ventricular arrhythmias. Although autologous bone marrow-derived cells show some evidence of improving left ventricular function, procedural variables such as cell type and timing of infusion must be explored and optimized. He noted also that no Phase 3 study has been completed to date, and placebo effects are seen in most published trials. Moreover, cell-based therapies do not halt the progression of disease in the patient populations studied. Furthermore, the mechanism by which these cells act is incompletely characterized, and the correct method to quantify their biologic activity in vivo is not known.


One attendee asked about the effects of timing cell delivery post-MI. Dr. Losordo noted that the later the cells are infused, the greater the magnitude of the benefit. Although this observation may seem counterintuitive, a delay of several days does not obviate the possibility of benefit. He noted that this observation suggests that the therapeutic window may be longer than initially assumed. However, the route of administration varies upon the setting and the flow of blood.

Another participant inquired about the cost per patient for such therapy. Dr. Losordo stated that the benefit may be modest at a cost $12,000-$17,000/patient. He noted that it will be critical to determine which subpopulations will benefit. With regard to complications, catheter-associated risks should be considered, although there have been no reports of autoimmune phenomena associated with these procedures.