ABSTRACT
Background: Intracoronary delivery of autologous bone marrow mononuclear cells is an interesting therapeutic promise for patients with heart failure of different etiologies. Aim: To evaluate the long-term safety and efficacy of this therapy in patients with dilated cardiomyopathy of different etiologies under optimal medical treatment. Patients and Methods: Prospective, open-label, controlled clinical trial. Of 23 consecutive patients, 12 were assigned to autologous bone marrow mononuclear cell intracoronary transplantation, receiving a mean dose of 8.19 ± 4.43 x 10(6) CD34+ cells. Mortality, cardiovascular readmissions and cancer incidence rate, changes in functional capacity, quality of life questionnaires and echocardiographic measures from baseline, were assessed at long-term follow-up (37.7 ± 9.7 months) in patients receiving or not the cells. Results: No significant differences were observed in mortality, cardiovascular readmissions or cancer incidence rate amongst groups. An improvement in functional class and quality of life questionnaires in the transplanted group was observed (p < 0.01). The treated group showed a non-significant increase in left ventricular ejection fraction at long-term follow-up (from 26.75 ± 4.85% to 34.90 ± 8.57%, p = 0.059 compared to baseline). There were no changes in left ventricular volumes. We observed no improvement of these variables in the control group. Conclusions: Intracoronary transplantation of autologous bone marrow mononuclear cells is feasible and safe in patients with dilated cardiomyopathy of diverse etiologies. This therapy was associated to persistent improvements in functional class and quality of life. There was also a non-significant long-term improvement of left ventricular function.
Subject(s)
Female , Humans , Male , Middle Aged , Bone Marrow Transplantation/methods , Cardiomyopathy, Dilated/surgery , Bone Marrow Transplantation/mortality , Cardiac Volume/physiology , Cardiomyopathy, Dilated/mortality , Cardiomyopathy, Dilated , Follow-Up Studies , Patient Readmission/statistics & numerical data , Prospective Studies , Quality of Life , Stroke Volume/physiology , Surveys and Questionnaires , Time Factors , Transplantation, Autologous , Treatment Outcome , Ventricular Function/physiologyABSTRACT
Available medical therapy is unable to completely prevent or revert the pathological cardiac remodeling secondary to ischemia or other injuries, which is responsible for the development of heart failure. Regenerative medicine through stem cells had an explosive development in the cardiovascular area during the past decade. Stem cells possess the capacity to regenerate, repair or substitute damaged tissue, allowing the reestablishment of its function. Stem cells can also modulate apoptosis, angiogenesis, fibrosis and inflammation, favoring the endogenous regenerative process initiated by the damaged tissue. These capacities have been corroborated in several animal models of cardiovascular diseases with positive results. In humans, therapies with bone marrow mononuclear stem cells, mesenchymal stem cells and cardiac stem cells are safe. Most randomized clinical trials in patients with myocardial infarction or cardiomyopathies of different etiologies have reported benefits on ventricular function, quality of life and even over mortality of treated patients. This article reviews the state of art of stem cell therapy in cardiovascular diseases, focusing on the most common cellular types used in patients with acute myocardial infarction and chronic cardiomyopathies of different etiologies.
Subject(s)
Humans , Cardiovascular Diseases/surgery , Stem Cell Transplantation/methods , Cell Transdifferentiation , Chronic Disease , Heart Diseases/surgery , Multipotent Stem Cells/physiology , Multipotent Stem Cells/transplantation , Myocardial Infarction/surgeryABSTRACT
Mesenchymal stem cells (MSCs) are now known to display not only stem cell multipotency, but also robust antiinflammatory and regenerative properties. After widespread in-vitro and in-vivo preclinical testing, autologous and allogeneic MSCs have been applied in a range of immune mediated conditions, including graft versus host disease, Crohn's disease, multiple sclerosis, refractory systemic lupus erythematosus and systemic sclerosis. Current data suggests that MSCs may not only replace diseased tissues, but also exert several trophic, regenerative and antiinflammatory effects. While the clinical outcome in case reports and phase I-II trials seems occasionally striking, these limited results point to the need to perform controlled multicenter trials. Future advances from stem cell science can be expected to pinpoint significant MSC subpopulations and/or stem cell markers for improved regenerative or immunoregulatory properties.