Intramyocardial Injection Of Cd133(+) Bone Marrow-Derived Stem Cells Improves Cardiac Function Long-Term In The Majority Of Selected Patients With End-Stage Ischemic Heart Disease.

Abstract To improve tissue regeneration of ischemic myocardium, autologous bone marrow-derived stem cells have been injected intramyocardially in 10 patients with end-stage ischemic heart disease. Approx. 60 – 380 ml of bone marrow were harvested from the posterior iliac crest and processed in the operating room under GMP conditions using the automated cell selection device CliniMACS. By using the Duesseldorf protocol, the intraoperative isolation of CD133+-stem cells (1.9−10.0 x 106 cells; purity up to 97%) was achieved in less than 3 hours. Following isolation, autologous CD133+-stem cells were injected in a predefined pattern into the myocardium. Cardiac function was assessed by cardiac MRI and echocardiography three, six, and nine months postoperatively. A significant improvement of cardiac function could be documented in 7 out of 10 patients: ejection fraction (EF) before treatment: 10–22% - after 3 months: 18–30% - after 6 months: 19–30%, after 9 months: 21–31%; left ventricular enddiastolic volume (LVEDV) before treatment: 210 ± 123 ml, after 3 months: 169 ± 80 ml, after 6 months: 162 ± 82 ml, after 9 months: 175 ± 70 ml; left ventricular enddiastolic diameter (LVEDD) before treatment: 79.2 ± 7 mm, after 3 months: 57.4 ± 3 mm, after 6 months: 59.4 ± 4 mm, after 9 months: 56.2 ± 5 mm, respectively. In two patients cardiac function improved only temporarily over the first three months, 1 patient died one month after surgery due to a non-cardiac cause. In conclusion, the sole intramyocardial injection of autologous CD133+-cells proved to be safe and led to a significant gain in heart function in 7 of 10 patients, thereby avoiding or postponing (“bridging”) alternative therapies such as heart transplantaton. The benefial effects of intramyocardially injected bone marrow-derived stem cells might be explained by direcct cellular effects including neovascularization and indirect effects including the formation of growth factors promoting tissue repair.