Abstract
Stem cell therapy for cardiac infarct regeneration has been widely used in clinical research. Despite the fact that important advances in this field have been reached, the observed recovery does not demonstrate new cardiac muscle formation. Benefits have been observed due to an improvement in neovascularisation. The main objective of this study was to determine if pre-differentiated stem cells into cells of myocardic lineage are capable of engraftment in animal models with induced cardiac infarct and are capable of truly differentiating into myocardiocytes. Bone marrow rat stem cells were pre-differentiated with 5-AZ. After 4 weeks, pre-differentiated stem cells express muscarinic 1, 2 and β adrenergic 2 receptors. Also, proteins such as sarcomeric α-actin, cardiac myosin heavy chain, desmin and vimentin were detected by immunocytochemistry. Cells were transplanted intracardialy in an ischemic cardiac rat model. Pre-differentiated or non differentiated cells were transplanted after 4 weeks post infarct induction. Histopathology of the hearts was made 2 weeks after cell transplantation. Typical granulated tissue, scare formation and neovascularisation were observed in both groups. However, in those hearts from rats inoculated with pre-differentiated cells many appeared atypical and were α-actin sarcomeric positive. These events suggest that pre-differentiated cells conserve some muscle characteristic traits in situ that at least last for two weeks after transplantation.
Highlights
Myocardial infarction is the leading cause of heart failure in developed countries
The results show heart function improvement after stem cells transplantation [1,2,3,4,5,6,7,8,9,10,11]
Primary culture of stem cells recovered from the rat bone marrow showed characteristic CPU formation after 12 days incubation in DMEM-F12 medium (Figure 1(a))
Summary
Myocardial infarction is the leading cause of heart failure in developed countries. Even advanced therapeutic measures are usually not sufficient to prevent left ventricular remodeling as they fall short of replacing necrotic cardiac myocytes. Recent insights into stem cell biology have changed our understanding of regenerative activities in the infarcted heart and have raised considerable hopes for novel therapeutic approaches aimed at cardiac myocyte replacement/regeneration through cell transplantation. Considering this fact, stems cells have been used for autologous transplant in several clinical trials for repair of the ischemic myocardium. The results show heart function improvement after stem cells transplantation [1,2,3,4,5,6,7,8,9,10,11] It remains unclear which stem cell(s) can contribute to these effects on the myocardium, and whether they do so by trans-differentiation or cell fusion [12]. It has been suggested that this improvement of heart function has been the result of angiogenic effects more than the generation of new cardiac muscle [13]
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