Transplantation of Autologous Bone Marrow-Derived Cells into the Myocardium of Patients Undergoing Coronary Bypass
DOI:
https://doi.org/10.1532/HSF98.20041034Abstract
Background: Animal studies suggest that cell transplantation, including bone marrow-derived cells, can ameliorate left ventricular remodeling following myocardial ischemia. Clinical evaluation of the potential benefits of this approach is limited by the lack of safety and feasibility studies. We have assessed the safety and feasibility of intramyocardial transplantation of autologous bone marrow-derived cells in patients undergoing coronary artery bypass graft (CABG) surgery.
Methods and Results: Between December 2001 and May 2002 7 patients, scheduled for CABG, consented to the trial. All had CABG using hypothermic cardiopulmonary bypass (CPB) and cold cardioplegic arrest. An average of 21 ´ 106 (8.6 ´ 106 to 35.1 ´ 106) nucleated cells, and 4.2 ´ 104 (2.5 104 to 8.1 ´ 104) CD34+ cells were injected into the anterior-lateral wall of the left ventricle, after discontinuation of cardiopulmonary bypass. The end points to assess safety included death, massive bleeding, electrocardiographic or biochemical evidence of myocardial infarction, ventricular dysrhythmia, myocardial perfusion, ventricular function, and the patients' functional status.
All patients recovered well without ventricular arrhythmia, bleeding, or other major peri-operative complications. The average intensive care unit (ICU) and hospital stay was 1 and 7 days, respectively. Repeat Technetium-99m myocardial perfusion stress imaging and echocardiography 6 weeks after surgery showed improvement in tissue perfusion, and an average improvement of left ventricular function of 13.5% 11.54% (the mean pre- and post-operative left ventricular EF were 32.5% 15.46% and 46% 18.55%, respectively). Twenty-four hours Holter monitoring showed no significant arrhythmia, 3 months post-operatively. All patients with narrow QRS complex showed no evidence of late potential, on signal-averaged electrocardiogram. At 4 to 9 months after surgery patients were in NYHA functional class "I".
Conclusions: This early clinical experience shows that autologous bone marrow-derived cell transplantation into myocardium is feasible and relatively safe. Further clinical trials to assess the role of cell transplantation for myocardial repair are required.
References
Barnett D, Granger V, Storie I, et al. 1998. Quality assessment of CD34+stem cell enumeration: experience of the United Kingdom NationalExternal Quality Assessment Scheme (UK NEQAS) using a unique stable whole blood preparation. Br J Hematol 102(2):553-65.nEl Oakley RM, Seow KK, Tang TP, et al. 2002. Whole bone marrow transplantation induces angiogenesis following acute ischemia. Redox Rep 7(4):215-8.nJackson KA, Majka SM, Wang H, et al. 2001. Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest 107(11):1395-1402.nKocher AA, Schuster MD, Szabolcs MJ, et al. 2001. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 7(4):430-6.nLaham RJ, Oettgen P. 2003. Bone marrow transplantation for the heart: fact or fiction? Lancet. 361(9351):11-2.nOrlic D, Kajstura J, Chimenti S, et al. 2001. Bone marrow cells regenerate infarcted myocardium. Nature 410(6829):701-5.nStrauer BE, Brehm M, Zeus T, et al. 2002. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 106:1913-8.nTerada N, Hamazaki T, Oka M, et al. 2002. Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature 416(6880):542-5.nYau TM, Tomita S, Weisel RD, et al. 2003. Beneficial effect of autologous cell transplantation on infarcted heart function: comparison between bone marrow stromal cells and heart cells. Ann Thorac Surg 75(1):169-76.nYing QL, Nichols J, Evans EP, Smith AG. 2002. Changing potency by spontaneous fusion. Nature 416(6880):545-8.n