Showing papers by "Kishore B.S. Pasumarthi published in 2007"
TL;DR: The potential of various donor cell types in myocardial repair, mechanisms underlying functional improvement in cell-based therapies, as well as potential interactions between pharmacological and cell- based therapies are discussed.
Abstract: Heart failure secondary to ischemic heart disease, hypertension, and myocardial infarction is a common cause of death in developed countries. Although pharmacological therapies are very effective, poor prognosis and shorter life expectancy of heart disease patients clearly indicate the need for alternative interventions to complement the present therapies. Since the progression of heart disease is associated with the loss of myocardial cells, the concept of donor cell transplantation into host myocardium is emerging as an attractive strategy to repopulate the damaged tissue. To this end, a number of donor cell types have been tested for their ability to increase the systolic function of diseased hearts in both experimental and clinical settings. Although initial clinical trials with bone marrow stem cells are encouraging, long-term consequences of such interventions are yet to be rigorously examined. While additional laboratory studies are required to address several issues in this field, there is also a clear need for further characterization of drug interactions with donor cells in these interventions. Here, we provide a brief summary of current pharmacological and cell-based therapies for heart disease. Further, we discuss the potential of various donor cell types in myocardial repair, mechanisms underlying functional improvement in cell-based therapies, as well as potential interactions between pharmacological and cell-based therapies.
34 citations
TL;DR: It is suggested that embryonic myocardial cell differentiation is a gradual process and undifferentiated cells expressing Nkx2.5 in post‐chamber myocardium may represent a progenitor cell population while cells expressingNkx 2.5 and ANF represent differentiating myocytes.
Abstract: The recent discovery of several myogenic cardiac progenitor cells in the post-natal heart suggests that some myocardial cells may remain undifferentiated during embryonic development. In this study, we examined the subcellular characteristics of the embryonic (E) mouse ventricular myocardial cells using transmission electron microscopy (TEM). At the ultrastructural level, we identified three different cell populations within the myocardial layer of the E11.5 heart. These cells were designated as undifferentiated cells (43 ± 6%), moderately differentiated cells (43 ± 2%) and mature cardiomyocytes (14 ± 4%). Undifferentiated cells contained a large nucleus and sparse cytoplasm with no myofibrillar bundles. Moderately differentiated cells contained randomly arranged myofilaments in the cytoplasm. In contrast, mature cardiomyocytes contained well-developed sarcomere structures. We also confirmed the presence of similar undifferentiated cells albeit at low levels in the E16.5 (∼20%) and E18.5 (∼7%) myocardium. Further we used immunogold labeling technique to test whether these distinct cell populations were also positive for markers such as Nkx2.5, ISL1 and ANF. A preponderance of anti-Nkx2.5 label was found in the undifferentiated and moderately differentiated cell types. Anti-ANF label was found only in the cytoplasmic compartment of moderately differentiated and mature myocardial cells. All of the undifferentiated cells were negative for anti-ANF labeling. We did not find immuno-gold labeling with ISL1 in any of the three myocardial cell types. Based on these results, we suggest that embryonic myocardial cell differentiation is a gradual process and undifferentiated cells expressing Nkx2.5 in post-chamber myocardium may represent a progenitor cell population while cells expressing Nkx2.5 and ANF represent differentiating myocytes.
27 citations