Myoblast Transplantation for Cardiac Repair: A Clinical Perspective

Abstract

The incidence of heart failure is achieving epidemic proportions. Adult human myocytes cannot regenerate because these cells do not re-enter the cell cycle. In patients with heart failure, myoblast transplantation is emerging as a potential therapeutic option to augment the function of remaining myocytes. Both skeletal myoblasts and autologous bone marrow cell transplantation, after intensive preclinical experimental animal studies, have entered phase I safety studies in humans. Most of these clinical trials have involved small groups of patients and cell transplantation was carried out as an adjunct to coronary revascularization. Preliminary results show that the procedure is safe and leads to improved myocardial function. This paper reviews and summarizes the outcome of these phase I trials involving skeletal myoblast transplantation.

Preconditioning and Stem Cell Survival

“…Similarly, treatment with insulin-like growth factor 1 (IGF-1), vascular endothelial growth factor, β-fibroblast growth factor, and heat shock stimulates cell survival after transplantation. Our experience with cross-species transplantation of human skeletal myoblasts showed that skeletal myoblasts were conditionally immunoprivileged and required transient immunosuppression during early phase of engraftment in the infarcted heart [34,36]. Similarly, the immunoprivileged status of bone marrow stem cells has been shown in many studies after transplantation into immunocompetent experimental animal models [75,99].…”

“…Beginning more than 15 years ago with the use of unipotent myogenic precursor cells from skeletal muscle [57,58] and terminally differentiated cardiomyocytes [57,58], heart cell therapy has progressed to the use of multipotent and pluripotent stem and progenitor cells [22,30,59,63,80,86,105,108,112,122]. Despite extensive experimental animal studies and a decade-long clinical assessment of stem and progenitor cells to regenerate the damaged myocardium [25,34,36], the choice of donor stem and progenitor cells and transplantation protocols for optimal prognosis still remain the focal issue in the use of stem cells for cardiac repair. Although various cell types have been assessed for their safety, feasibility, and efficacy, the discovery of the presence of resident cardiac stem and progenitor cells and their successful isolation and propagation in vitro for transplantation has significantly moved the field of stem cell research [8,82].…”

Cardiac Bodies: A Novel Culture Method for Enrichment of Cardiomyocytes Derived from Human Embryonic Stem Cells

“…Recent investigations of cell transplantation in animal models and clinical trials have stimulated the hope that impaired cardiac function may be improved through cell replacement therapy (for examples, see refs. [1][2][3][4][5][6][7][8][9][10][11][12][13].…”

Development of Bioartificial Myocardium Using Stem Cells and Nanobiotechnology Templates

“…The encouraging results of experimental studies [6][7][8][9][10] have opened the way to the clinical application of cellular cardiomyoplasty in patients with akinetic and nonviable postinfarction scar and low ejection fraction and in patients presenting idiopathic and chagasic cardiomyopathies [11][12][13][14]. Cultured autologous cells do not raise immunological, ethical, tumorogenesis, or donor availability problems.…”