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Regeneration of Human Infarcted Heart Muscle by Intracoronary Autologous Bone Marrow Cell Transplantation in Chronic Coronary Artery Disease

The IACT Study

Bodo E. Strauer, MD^_*,_*, Michael Brehm, MD^_*, Tobias Zeus, MD^_*, Thomas Bartsch, MD^_*, Christina Schannwell, MD^_*, Christine Antke, MD, Rüdiger V. Sorg, PhD, Gesine Kögler, PhD, Peter Wernet, MD, Hans-Wilhelm Müller, MD and Matthias Köstering, MD^_*

^_* Department of Internal Medicine, Division of Cardiology, Pneumology and Angiology, Heinrich-Heine-University, Düsseldorf, Germany
Department of Nuclear Medicine, Heinrich-Heine-University, Düsseldorf, Germany
Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine-University, Düsseldorf, Germany

View larger version (24K): [in a new window]   Figure 1 Diagrammatic representation of the algorithm of intracoronary stem cell therapy (Tx) in chronic ischemic heart disease after myocardial infarction. The infarcts occurred 27 ± 31 months before Tx. All infarct patients were treated with percutaneous transluminal coronary angioplasty (PTCA) or with stent implantation. 9 ± 6 months before (investigation 1) coronary angiography (including quantitative left ventriuclography) was performed. If re-stenosis was present, re-PTCA was made. Investigation 2 embraces all patients for the evaluation of coronary morphology after PTCA/stent. Only patients with an open infarct-related artery were included in both groups. Patients who agreed to Tx received within 10 days after investigation 2 bone marrow punctures and Tx by the intracoronary administration route and had altogether five invasive investigations, including two for therapeutic reasons (nos. 0 and 1). Patients who were not eligible for Tx (disagreement with bone marrow puncture and with subsequent Tx) served as a control group. Investigation 3 represents all follow-up measurements 3 months after Tx (Tx patients) or after investigation 2 for control group patients.

View larger version (40K): [in a new window]   Figure 2 Representative illustration of 18F-FDG-positron emission tomography (PET) before (above) and 3 months after (below) cell therapy in the transversal (left) and longitudinal (right projection) in a 30-year-old male patient with an 8-month-old anteroapical infarction. Note the restoration of glucose uptake (below) within the infarcted area of the formerly completely avital anteroapical myocardium.

View larger version (37K): [in a new window]   Figure 3 Illustration of the mean values of (A) area of infarction, (B) ejection fraction, and (C) infarction wall movement velocity, determined by quantitative left ventriculography in both groups (control group vs. transplantation [Tx] group) at the point of time: investigations 1, 2, and 3. Comparision of both groups with chronically infarcted myocardium (conrol group vs. Tx group), n = 18 patients. Investigation 1 was 9 ± 6 months before cell transplantation (controls: 9 ± 5 months before percutaneous transluminal coronary angioplasty [PTCA]); investigation 2 within 10 days before cell tranplantation (controls: at the time point of PTCA) and investigation 3 was three months after cell transplantation (controls: 8 ± 5 months after PTCA). Note the significant decrease of infarct size and the increase in ejection fraction and in contractility (infarction wall movement velocity) 3 months after cell therapy in comparison with the control group. *p = not significant (investigation 2 vs. investigation 3); #p = 0.001 (investigation 2 vs. investigation 3).

View larger version (12K): [in a new window]   Table 4 Positron Emission Tomography and Spiroergometry Before and After Stem Cell Therapy in Chronically Infarcted Myocardium