Intramyocardial Injection of Autologous Bone Marrow Cells as an Adjunctive Therapy to Incomplete Myocardial Revascularization - Safety Issues

Abstract

OBJECTIVES: To determine the safety of intramyocardial injection of autologous bone marrow cells in patients undergoing surgical myocardial revascularization (CABG) for severe coronary artery disease. INTRODUCTION: There is little data available regarding the safety profile of autologous bone marrow cells injected during surgical myocardial revascularization. Potential risks include arrythmias, fibrosis in the injected sites and growth of non-cardiac tissues. METHODS: Ten patients (eight men) were enrolled; they were 59&plusmn;5 years old with limiting angina and were non-optimal candidates for complete CABG. Bone marrow cells (1.3&plusmn;0.3x10(8)) were obtained prior to surgery, and the lymphomonocytic fraction (CD34+=1.8&plusmn;0.3%) was separated by density gradient centrifugation. During surgery, bone marrow cells were injected in non-grafted areas of ischemic myocardium. During the first year after surgery, the patients underwent laboratory tests, cardiac imaging, and 24-hour ECG monitoring. RESULTS: Injected segments: inferior (n=7), anterior (n=2), septal (n=1), apical (n=1), and lateral (n=1) walls. Except for a transient elevation of C-reactive protein at one month post-surgery (P=0.01), laboratory tests results were within normal ranges; neither complex arrhythmias nor structural abnormalities were detected during follow-up. There was a reduction in functional class of angina from 3.6&plusmn;0.8 (baseline) to 1.2&plusmn;0.4 (one year) (P<0.0001). Also, patients had a significant decrease in the ischemic score assessed by magnetic resonance, not only globally from 0.65&plusmn;0.14 (baseline) to 0.17&plusmn;0.05 (one year) (P=0.002), but also in the injected areas from 1.11&plusmn;0.20 (baseline) to 0.34&plusmn;0.13 (one year) (P=0.0009). CONCLUSIONS: Intramyocardial injection of bone marrow cells combined with CABG appears to be safe. Theoretical concerns with arrhythmias and/or structural abnormalities after cell therapy were not confirmed in this safety trial

Clinical profile of patients enroled in a cell therapy trial for severe coronary artery disease

“…A total of 67 patients (61 SD 9 years, 82% men) with multivessel CAD referred for surgical myocardial revascularisation were included in this case–control study in which patients in the cell therapy group served as ‘cases’ (BMC Group; n = 34) were compared with patients in the CABG group (‘controls’). Patients in the BMC Group were recruited from a prospective, open‐label, uncontrolled, phase I clinical trial using adult autologous BMC combined to incomplete myocardial revascularisation for severe, advanced CAD as reported elsewhere (Gowdak et al. 2008).…”

Early Increase in Myocardial Perfusion After Stem Cell Therapy in Patients Undergoing Incomplete Coronary Artery Bypass Surgery

“…A 1-mL sample of the cell suspension was used for cell counting before injection (using the Türk's solution) and sorting by flow cytometry using leukocyte differentiation markers. Based on available clinical studies [22][23][24][25][26], we decided that at least 1×10 8 cells should be injected per patient. Cell viability by the Trypan blue exclusion test was greater than 90%.…”

“…The results reported so far demonstrated not only an increase in left ventricular ejection fraction (LVEF) [22] and wall motion score index [23] but also an increase in infarct tissue perfusion after autologous stem cell therapy in patients undergoing CABG [24,25]. A comprehensive safety analysis was performed previously and no adverse effects had been linked to the intramyocardial injection of autologous BMC during bypass surgery [26]. Therefore, we conducted this open-label, non-randomized study to test the hypothesis that intramyocardial injection of autologous BMC may help increase myocardial perfusion early on in patients undergoing incomplete surgical myocardial revascularization for severe IHD and diffuse CAD, irrespective of the degree of the completeness of the revascularization.…”

Advancing radiology through informed leadership: summary of the proceedings of the Seventh Biannual Symposium of the International Society for Strategic Studies in Radiology (IS3R), 23–25 August 2007

“…Various imaging techniques, including MRI, PET, and SPECT, have been used to assess the functional effects of cell therapy, and methods for tracking and labeling cells with radionuclides and superparamagnetic agents are being developed [ 9 ]. Although extensive clinical trials are still needed, cellular therapy could potentially become an important alternative to heart transplantation for the vast numbers of patients suffering from severe heart disease [ 10 ].…”