Injection Of Autologous Bone Marrow Mononuclear Cells Research Articles

Cardiomyopathy and Cell Therapy: Ejection Fraction Improvement and Cardiac Muscle Mass Increasing, after a Year of Bone Marrow Stem Cells Transplantation, by Magnetic Resonance Image

The idiopathic dilated cardiomyopathy (IDC) is one of the major public health problems in the western world. Patients with IDC in functional class IV (New York Health Association - NYHA), even after therapeutic optimization, have high mortality. Stem cell therapy has emerged as a potential therapeutic option for cell death-related heart diseases and several positive effects were assigned to cell therapy in cardiomyopathy. The aim of this study was identify short-term result of cell transplantation in idiopathic dilated cardiomyopathy patients (IDC) who were treated by transplantation of autologous bone marrow mononuclear cells (BMMC). Intracoronary injections of autologous BMMC were performed in eight patients with severe ventricle dysfunction (mean of left ventricle ejection fraction – LEVF=20.03%), cardiac mass muscle around 156.2 g and NYHA between III and IV grades, other 8 IDC patients received placebo. The IDCs were followed - up for one and two years, by magnetic resonance imaging (MRI). The results after one year showed significant improvement in LVEF (mean=181.4) and muscle mass increasing (mean=181.4 g), after two years the LVEF continued improving, reaching a mean of 32.69% and the cardiac muscle mass kept stable (mean=179.4 g). Excepted for one patient, all the other had improvement in the NYHA functional class. The placebo group did not show any improvement. We believe that BMMC implant may be a beneficial therapeutic option for IDC patients.

Heart to Heart

The notion of cell transplantation into the heart as a means of reversing ischemic injury is now nearly a decade old. The first clinical application of bone marrow mononuclear cells (BMCs) for myocardial infarction was in 2001,1 presumably motivated at least in part by the premise that BMCs injected into the heart can directly regenerate new, functional myocardium.2 Although subsequent investigators questioned the ability of BMCs to transdifferentiate into cardiomyocytes3,4 (but in all fairness, others did support the idea5,6), the horse was out of the barn, and the treatments continued apace. Fortunately, injection of autologous BMCs as adjunctive treatment for convalescent myocardial infarction has proven to be remarkably safe.7–9 Although the overall efficacy is modest, certain subgroups (particularly those with large functional deficits at baseline) do experience clinically meaningful increments in ejection fraction.10,11 A related consideration arises in the choice of cell type to transplant. BMCs, although easy to harvest, are almost certainly not the best candidate cells for cardiomyoplasty, because they are not specialized to regrow normal healthy heart muscle. An attractive alternative arose with the recognition that the adult heart contains its own reservoir of progenitor cells,12–15 some of which express the stem cell antigen c-kit.12,14 Such cardiac progenitor cells (CPCs) presumably function physiologically to mediate a low basal turnover rate of cardiomyocytes in the adult heart16 but may be expanded and exploited iatrogenically for more focused (and, mechanistically, more rational) benefit than may be possible with BMCs. When injected into the injured heart, CPCs increase tissue viability12,14,17–20 and improve ventricular function.12,14,17,20 Articles see p 1992 and p 2001 Ironically, we are now less certain about the mechanism of cell therapy than we thought we were a decade ago, when it seemed that direct regeneration of tissue …

Autologous bone marrow-derived progenitor cell myocardial delivery for recent myocardial infarction patients following early angioplasty: results from a pilot study

Cellular cardiomyoplasty is a potential therapeutic approach to preventing left ventricular remodeling after myocardial infarction and has shown encouraging results such as induction of neoangiogenesis and functional improvement of diseased hearts. We report the results of a pilot study on progenitor cells in five patients with acute myocardial infarction (AMI). Patients with single-vessel disease who had their first episode of myocardial infarction and underwent angioplasty after 48 h (an average of 17 days following myocardial infarction) were included in the study. Mononuclear cells (MNCs) (1x10(7)) were isolated by Ficoll Hypaque method from 60 ml of bone marrow (BM) obtained from the iliac crest of 5 patients (aspiration was performed under local anesthesia). The mean CD34 count was 1-4%. After confirming the patency of the affected vessel postangioplasty, cellular concentrate was injected into the affected artery in 3-ml boluses (three to four injections), with intermittent occlusion. The mean age of all five male patients was 48.6+13.7 years. At 1 year, five patients were asymptomatic, and one had Class II dyspnea on exertion. The results of an echocardiogram performed at 6 months showed an improvement in ejection fraction (EF) from 35.3% to 43.13% and in fractional shortening from 24.75% to 28.33%. End-systolic volume decreased from 115.5 to 92.3 ml, end-diastolic volume decreased from 177.5 to 170 ml, and end-systolic dimensions also decreased from 4.26 to 4 mm, demonstrating positive left ventricular remodeling. Repeat echocardiogram at 1 year showed persistent improvement in EF. No adverse events were noted either before or after the procedure. The injection of autologous BM MNCs is a safe and efficacious therapy following early revascularization in AMI patients.

864-2 One-year follow-up of transendocardial injection of autologous bone marrow mononuclear cells for ischemic cardiomyopathy

Emerson C. Perin, Hans F. Dohmann, Radovan Borojevic, Suzana A. Silva, Andre L. Sousa, Guilherme V. Silva, Joao A. Assad, Claudio T. Mesquita, Luciano Belem, Roberto Esporcatte, Fernando O. Rangel, Antonio C. Carvalho, Isabel Rossi, William K. Vaughn, Hans J. Dohmann, James T. Willerson, Texas Heart Institue, Houston, TX, Pro-Cardiaco Hospital, Rio de Janeiro, BrazilBackground: Limited treatment options exist for patients with end-stage ischemic heartfailure (HF) not amenable to revascularization. We evaluated the effect of transendocar-dial (TE) delivery of Autologous Bone Marrow Mononuclear Cells (ABMMC) in patientswith severe HF.Methods: Ten patients (mean age 58 ± 11 yrs) were studied. All patients had LV dysfunc-tion secondary to ischemic cardiomyopathy. Bone marrow (50 ml) was aspirated andABMMCs were isolated. TE injections were performed using the Myo-star catheter(NOGA, Biosense) to target hibernating myocardium guided electromechanical mapping(EMM). Patients were evaluated by ramp treadmill and Holter monitoring at baseline, 2months , 6 months and one year. ANOVA was utilized.Results: Exercise testing showed gradual and continous improvement in METs(p=0.0005) and VO2max (p=0.002) over time . MET's improved from 4.9 at baseline to6.7 at 2 months to 7.4 at 6 months up to 7.9 at one year follow-up. There was no differ-ence in total number of PVC's over the follow-up period. Ramp treadmill findings ofVO2max are presented in figure 1.Conclusion: In this small number of patients receiving TE injection of ABMMC and fol-lowed up to one year there was no evidence of significant arrhythmias and there was sus-tained improvement in exercise capacity. Future studies are needed to further clarify therole of stem-cell therapy in the treatment of ischemic cardiomyopathy.