Transendocardial, Autologous Bone Marrow Cell Transplantation for Severe, Chronic Ischemic Heart Failure

Abstract

Background-This study evaluated the hypothesis that transendocardial injections of autologous mononuclear bone marrow cells in patients with end-stage ischemic heart disease could safely promote neovascularization and improve perfusion and myocardial contractility. Methods and Results-Twenty-one patients were enrolled in this prospective, nonrandomized, open-label study (first 14 patients, treatment; last 7 patients, control). Baseline evaluations included complete clinical and laboratory evaluations, exercise stress (ramp treadmill), 2D Doppler echocardiogram, single-photon emission computed tomography perfusion scan, and 24-hour Holter monitoring. Bone marrow mononuclear cells were harvested, isolated, washed, and resuspended in saline for injection by NOGA catheter (15 injections of 0.2 cc). Electromechanical mapping was used to identify viable myocardium (unipolar voltage Ն6.9 mV) for treatment. Treated and control patients underwent 2-month noninvasive follow-up, and treated patients alone underwent a 4-month invasive follow-up according to standard protocols and with the same procedures used as at baseline. Patient population demographics and exercise test variables did not differ significantly between the treatment and control groups; only serum creatinine and brain natriuretic peptide levels varied in laboratory evaluations at follow-up, being relatively higher in control patients. At 2 months, there was a significant reduction in total reversible defect and improvement in global left ventricular function within the treatment group and between the treatment and control groups (Pϭ0.02) on quantitative single-photon emission computed tomography analysis. At 4 months, there was improvement in ejection fraction from a baseline of 20% to 29% (Pϭ0.003) and a reduction in end-systolic volume (Pϭ0.03) in the treated patients. Electromechanical mapping revealed significant mechanical improvement of the injected segments (PϽ0.0005) at 4 months after treatment. Conclusions-Thus, the present study demonstrates the relative safety of intramyocardial injections of bone marrowderived stem cells in humans with severe heart failure and the potential for improving myocardial blood flow with associated enhancement of regional and global left ventricular function. (Circulation. 2003;107:2294-2302.)

Mesenchymal stem cells are superior to angiogenic growth factor genes for improving myocardial performance in the mouse model of acute myocardial infarction

“…Rare studies used the human MSCs to treat myocardial infarction in mice model. Although bone marrow mononuclear cells have been used in clinical trials [28][29][30][31], these cells are not purified MSC population. Moreover, these trials using bone marrow mononuclear cells are not without risks [32][33][34].…”

Effect of intramyocardial bone marrow cell injection on diastolic function in patients with chronic myocardial ischemia

“…Initial studies demonstrated that intramyocardial bone marrow cell injection in patients with chronic ischemia is safe and improves myocardial perfusion (2-7). In addition, three studies observed a moderate improvement in left ventricular systolic function (4,5,7). However, the effect of intramyocardial bone marrow cell injection on left ventricular diastolic function has not been addressed thus far.…”

Medicina regenerativa con células madre adultas

“…Un total de 1,5 × 10 6 células purificadas de sangre perifé-rica, con el marcador AC133+ (mesenquimales y multipotentes), se inyectaron en la región periinfarto, obteniendo a los 9-16 meses una mejoría funcional de la fracción de eyección del ventrículo izquierdo (FEVI) y la perfusión. En otro estudio se evaluaron 14 pacientes con disfunción ventricular intensa de origen isquémico, a los que se inyectó una población celular de medula ósea seleccionada (CD34+CD45+) de forma transendocárdica mediante un sistema de catéter guiado 19 . A los 2 meses se encontró una mejoría de la perfusión y función ventricular global.…”