[Frontiers in Bioscience E3, 506-514, January 1, 2011]

Safety and efficacy of bone marrow-derived autologous CD133+ stem cell therapy

Dale S. Adler1, Hillard Lazarus2, Ravi Nair3, Jonathan L. Goldberg2, Nicholas J. Greco2,4, Tom Lassar2, Mary J. Laughlin2,4,5, Hiranmoy Das6, Vincent J. Pompili6

1Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 2Department of Medicine, University Hospitals Case Medical Center, Cleveland, OH, 3Department of Medicine, Cleveland Clinic Foundation, Cleveland, OH, 4The Cleveland Cord Blood Center, Cleveland OH, 5University of Virginia, Charlottesville, VA, 6Department of Medicine, The Ohio State University Medical Center Hospital, Columbus, OH

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Methods
3.1. Patient selection
3.2. Study design and parameters of safety
3.3. Cell preparation and delivery
3.4. Evaluation of safety and feasibility
3.5. Pharmacologic stress test and 99mTc-sestamibi assessments
3.6. Angina assessment
3.7. Statistics
4. Results
4.1. Baseline characteristics
4.2. Procedural and cellular characteristics
4.3. Outcomes
5. Discussion
5.1. Limitations
6. Conclusion
7. Acknowledgements
8. References

1. ABSTRACT

The Phase I clinical study was designed to assess the safety and feasibility of a dose escalating intracoronary infusion of autologous bone marrow (BM)-derived CD133+ stem cell therapy to the patients with chronic total occlusion (CTO) and ischemia. Nine patients were received CD133+ cells into epicardial vessels supplying collateral flow to areas of viable ischemic myocardium in the distribution of the CTO. There were no major adverse cardiac events (MACE), revascularization, re-admission to the hospital secondary to angina, or acute myocardial infarction (AMI) for the 24-month period following cellular infusion. In addition, there were no periprocedural infusion-related complications including malignant arrhythmias, loss of normal coronary blood flow or acute neurologic events. Cardiac enzymes were negative in all patients. There was an improvement in the degree of ischemic myocardium, which was accompanied by a trend towards reduction in anginal symptoms. Intracoronary infusion of autologous CD133+ marrow-derived cells is safe and feasible. Cellular therapy with CD133+ cells to reduce anginal symptoms and to improve ischemia in patients with CTO awaits clinical investigation in Phase II/III trials.