Cellular cardiomyoplasty: current state of the field.

Cellular cardiomyoplasty employs stem cell therapy to regenerate myocardium. Characterized by their potential for proliferation, differentiation and capacity for self-renewal, stem cells are ideally suited for use in regenerative medicine. Supplementing traditional therapeutic modalities aimed at the palliation of congestive heart failure, cellular cardiomyoplasty is an innovative approach aimed at producing functional, viable myocardium following an acute infarction. The primary focus is to prevent the onset of congestive heart failure; however, potential applications aimed at reversing ischemic heart disease are concurrently in development. After decades of research, cellular cardiomyoplasty has moved beyond traditional in vitro and animal models; it is currently being implemented in clinical trials. Despite this monumental advance, certain limitations remain inherent in this process, preventing stem cell therapy from reaching its full potential. On a cellular level, stem cell retention and viability postimplantation continues to be problematic. Solutions under investigation include pioneering advances in cell delivery, in vitro pretreatment, and tissue engineering. Moreover, questions surrounding optimal cell type and cellular mechanisms concerning cellular cardiomyoplasty remain unanswered. Clarification of these issues is essential to ensure continued progression of this new technology. Stem cell therapy has been highly successful within the in vitro and in vivo environment. However, as clinical trials abound, cellular cardiomyoplasty must transition from an experimental concept to an effective therapeutic treatment. This process is hindered by discordance between scientific accrue and practical applicability. This review will provide a comprehensive summary of current innovations on cellular cardiomyoplasty, and future prospects. There will be a particular emphasis on the clinical aspects of stem cell therapy in an attempt to bridge the gap between science and medicine. Overcoming this barrier will render cellular cardiomyoplasty accessible to patients on a global basis.

Técnica de cultivo de mioblastos autólogos humanos para transplante clínico / Technique of culture of human autologous mioblasts for clinic transplant

Introducción: El trasplante celular para reparar o regenerar el miocardio dañado es un nuevo objetivo en la enfermedad cardiovascular. Los mioblastos esqueléticos autólogos son las células más estudiadas y constituyen la primera elección para la reparación cardíaca. Objetivos: Puesta a punto de la técnica de cardiomioplastia celular en muestras obtenidas de donantes multiorgánicos y llevar a cabo esta técnica junto con la revascularización en dos pacientes. Material y métodos: Se han obtenido 15 biopsias de músculo vasto lateral de donantes multiorgánicos y de dos pacientes con infarto de miocardio no reciente. Después de tres semanas de cultivo, se evaluó en todas las muestras el porcentaje de mioblastos con los anticuerpos CD56, desmin y miogenin. Los dos pacientes fueron sometidos a cirugía de revascularización e inyección intramiocárdica de mioblastos esqueléticos autólogos obtenidos tras cultivo con suero autólogo. Resultados: Se demostró la presencia de un gran número de células positivas con los marcadores desmina y miogenin. El implante de mioblastos esqueléticos autólogos no se asoció con el desarrollo de efectos adversos. Conclusiones: En pacientes con un infarto de miocardio no reciente, el tratamiento con mioblastos en conjunción con bypass arteria coronaria es seguro y fácil y es relativamente fácil obtener mioblastos de tejido muscular para trasplantar (AU)

Introduction: Cellular transplant to repair or regenerate damaged myocardium is a new objective in cardiovascular disease. The autologous skeletal myoblasts are the most studied cells and constitute the first election for cardiac repair. Objectives: fine adjustment of the cellular cardiomyoplasty technique with revascularization in two patients. Material and methods: 15 biopsies were obtained from multiorganic donors and from two patients with no recent infarct. After three weeks of culture, the percentage of myoblasts were evaluated using monoclonal antibodies CD56, desmin and myogenin. The two patients were subjected to revascularization surgery and intramyocardic injection of autologous skeletic myoblasts obtained after culture with autologous serum. Results: The presence of a great number of positive cells with desmin and myogenin markers was shown. The implantation of autologous skeletal myoblasts was not associated with the development of adverse effects. Conclusions: In patients without a recent myocardium infarct, the treatment with myoblasts together with coronary artery bypass is sure and easy and it is straightforward to obtain myoblasts from muscle tissue for transplant (AU)

Stem cell transplantation for the treatment of myocardial infarction.

Stem cell transplantation provides a potential regenerative therapy for the heart damaged by myocardial infarction. Numerous scientific studies have been undertaken in animals and humans to analyze the safety and efficacy of this new approach. However, at the present time, the results have been mixed and inconclusive, and the mechanism of stem cell transplantation therapy remains unclear. This review discusses the controversies and problems that need to be addressed in future investigations.

Bone marrow cells in the repair and modulation of heart and blood vessels: emerging opportunities in native and engineered tissue and biomechanical materials.

Adult bone marrow-derived stem/progenitor cells have traditionally been considered to be tissue-specific cells with limited capacity for differentiation. However, recent discoveries have generated tremendous excitement regarding possible applications of stem cells, particularly bone marrow-derived stem cells, in the treatment of human diseases. The potential ability to regenerate cells of various different lineages has raised the therapeutic possibility of using these bone marrow-derived stem cells as a source of cells for tissue repair and regeneration. Tissue engineering is a rapidly expanding interdisciplinary field aimed at restoring function to tissues through the delivery of constructs which become integrated into the patient. The use of bone marrow-derived stem cells provides a less invasive source for cells applicable to tissue engineering, including cardiovascular tissues such as heart valves, blood vessels, and myocardium. Although these strategies are in the early stages of development, they are conceptually promising and offer important insights into the future treatment of various cardiovascular ailments.

Cardiocirculatory bio-assist: is it time to reconsider demand dynamic cardiomyoplasty? Review and future perspectives.

In the last 15 years, dynamic cardiomyoplasty has remained an experimental procedure even after the enthusiastic short- and mid-term results, mainly because of the disappointing long-term outcome caused by muscular degeneration secondary to chronic continuous electrical stimulation of the latissimus dorsi. In Italy, a group of muscular pathologists, cardiologists, and cardiac surgeons conducted an experiment of an activity-rest stimulation protocol in humans that should avoid complete transformation of the skeletal muscle, maintaining its properties overtime. This "demand" stimulation protocol gave good results, improving New York Heart Association class, ejection fraction value, and survival. Even though dynamic cardiomyoplasty was excluded from the recent international guidelines for the management of heart failure, the discussion on the ability of this unique kind of cardiocirculatory bio-assistance is due to be reopened, thanks to the results of the new stimulation protocol. Heart transplantation, circulatory supporting devices, multisite stimulation therapy, and the total artificial heart are not always and in all countries the best solutions: the great economic cost, the numerous contraindications, the need for immunosuppression and antithrombotic therapy, and the troublesome follow up constitute important drawbacks. For patients in whom transplant surgery cannot be performed, as well as in developing countries, the nonprohibitively expensive demand dynamic cardiomyoplasty may still play a role.

New advances in dynamic cardiomyoplasty: Doppler flow wire shows improved cardiac assistance in demand protocol.

No data have been published on real cardiac assistance with demand dynamic cardiomyoplasty. We tested the utility of a Doppler flow wire in measuring beat by beat aortic flow velocity and evaluating cardiac assistance in demand cardiomyoplasty patients. The technique was tested in seven patients (M/W = 6/1; age, 57.1+/-6.2 years; atrial fibrillation/ sinus rhythm = 1/6; New York Heart Association [NYHA] classification = 1.4+/-0.5). Measurements were done using a 0.018 inch peripheral Doppler flow wire advanced through a 5 French arterial femoral sheath. Three 1 minute periods with the stimulator off, and three 1 minute periods with clinical stimulation were recorded. We measured peak aortic flow velocity in all beats. Latissimus dorsi mechanogram was simultaneously recorded. Comparison between preoperative and follow-up data showed significantly higher values of tetanic fusion frequency and ejection fraction at follow-up, whereas mean NYHA class was significantly lower. Statistical analysis showed an increase in aortic flow velocity not only in the assisted versus rest period, but also in assisted versus unassisted beats (8.42+/-6.98% and 7.55+/-3.07%). A linear correlation was found between increase in flow velocity and latissimus dorsi wrap tetanic fusion frequency (r2 = 0.53). In demand dynamic cardiomyoplasty, systolic assistance is significant and correlated to the latissimus dorsi speed of contraction; a demand stimulation protocol maintains muscle properties and increases muscle performance.

Surgical therapies for heart failure.

Heart transplantation remains the best hope for patients with end-stage heart failure unresponsive to conventional therapy, but the number of transplant candidates continues to exceed the number of available donor hearts. Despite major advances in the medical management of heart failure, researchers continue to explore alternative surgical therapies designed to augment cardiac function. Many of these surgical therapies are still in the experimental or clinical trial phases. Surgical approaches include coronary revascularization, mitral valve repair or replacement, cardiomyoplasty, left ventricular volume reduction surgery, and bridging to recovery with the use of ventricular assist devices. Although cardiac surgeons have gained considerable experience in the treatment of patients with heart failure, many improvements and innovations lie ahead.

Permanent cardiac assistance from skeletal muscle: a prospect for the new millennium.

This paper looks at the prospects for new surgical solutions to the problem of end-stage heart failure based on cardiac assistance from skeletal muscle. The current status of the main biological approaches, cardiomyoplasty, aortomyoplasty, and the skeletal muscle ventricle, are discussed, followed by a consideration of some of the important basic issues that need to be addressed if these techniques are to achieve their full potential. Although there is a review element to the paper, the main emphasis is on the work of our own research group and collaborating workers.

[Cellular cardiomyoplasty: state of the art, evaluation, and future possibilities]. / Cardiomyoplastie cellulaire. Etat des lieux, évaluation et avenir.

Cellular cardiomyoplasty, or the transplantation of myogenic cells into the myocardial tissues, could emerge as a therapeutic alternative in patients with cardiac failure. It depends on several procedures: implantation of cell types, syngenic embryonic cardiomycocytes, allogenic and autogenic cardiac muscle cells. These cells carne into contact with host cardiomyocytes and could contract in a synchronous fashion. Experimental data suggests that this technique could improve global left ventricular function in the post-infarction period or in dilated cardiomyopathy even though the precise mechanism of this improvement is not fully understood. Many difficulties remain, the cell types have an oncogenic potential; syngenic foetal cells are weakly immunogenic but their use is limited by ethical and problems of supply. Therefore, auto-transplantation either of cardiomycocytes obtained by endomyocardial biopsy or of adult skeletal muscle, could be a potential clinical option.

Radical alternatives to transplantation.

Because of the lack of donor hearts, thousands of patients annually die with end-stage heart failure. Surgical alternatives to transplantation include partial left ventricular resection, dynamic cardiomyoplasty, and left ventricular assist devices. Partial left ventricular resection is an innovative procedure in which the heart is surgically reduced in size and cardiac function is dramatically improved immediately after surgery. Long-term follow-up is required to determine the success of this procedure. Dynamic cardiomyoplasty has been in use for 12 years. In properly selected patients, it results in significant amelioration of symptoms and improvement in quality of life. Improved survival and objective physiologic improvement have not been documented. A randomized trial is now in progress to evaluate survival with surgical therapy versus survival with medical therapy. Left ventricular assist devices have been shown to be extremely effective as a short- and long-term "bridge" to heart transplantation in mortally ill patients. They are not approved for long-term support as an alternative to transplantation in the United States, but a randomized trial is now underway to compare the efficacy of these devices with the efficacy of medical therapy in New York Heart Association functional class IV patients.

Cardiomyoplasty--the beginning of a new era.

Cardiomyoplasty is a surgical treatment for a well-defined group of patients who suffer from congestive heart failure. The procedure is not a contraindication to perform a future heart transplantation, when indicated. The clinical results up to 7 years after cardiomyoplasty are encouraging, but there is still a gap between the significant functional capacity improvement of the patients after cardiomyoplasty and the moderate hemodynamic change. Experimental data and recent measurements in patients provide new insights in understanding the physiologic effect of cardiomyoplasty.

Myoplasty--a surgical option for end-stage heart failure.

Congestive heart failure is a growing problem in the Western world, which modern therapeutic options are doing little to ameliorate. Dynamic cardiomyoplasty may be one option which has great potential. This article reviews the use of skeletal muscle for circulatory assist and suggests that, with further work, it should take a significant place in the treatment armamentarium.

Cardiomioplastia, una alternativa al manejo de la falla cardíaca / Cardiomyoplasty, an alternative in heart failure management

Sin lugar a dudas el trasplante cardíaco constituye la terapia de elección para el manejo de los pacientes con falla cardíaca terminal refractaria al tratamiento médico. Sin embargo,la escasez de donantes,las crecientes listas de espera y los problemas relacionados con su manejo postoperatorio han llevado a la búsqueda de alternativas terapéuticas,que desde hace algunos años se han venido desarrollando en distintos centros del mundo. Una de las más interesantes es la cardiomioplastia,en la que se encuentra trabajando nuestro equipo de cirugía cardiovascular.En esta revisión tocaremos algunos de los aspectos más importantes de su evolución y desarrollo clínico.