Molecular Genetic Advances in Cardiovascular Medicine

Anversa, Piero; Sussman, Mark A.; Bolli, Roberto

doi:10.1161/01.cir.0000132469.85026.46

Cited by 62 publications

(29 citation statements)

References 41 publications

(58 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, despite the evidence that cell fusion occurs both in vivo and in vitro, [23][24][25][26][27][28][29][30][31] its frequency has been suggested to be lower than would be required to have a significant regenerative effect. 49 The clinical results are consistent with the in vitro observations. As in similar studies, 15,16,22 we found that autologous BMCs intracoronary transplantation after MI significantly reduces LV remodeling and improves both global and segmental cardiac performance.…”

Section: Discussionsupporting

confidence: 85%

Experimental and Clinical Regenerative Capability of Human Bone Marrow Cells After Myocardial Infarction

Fernández‐Avilés

Román

García-Frade

et al. 2004

Circulation Research

430

193

View full text Add to dashboard Cite

Abstract-Bone marrow mononuclear cells (BMCs) from 20 patients with extensive reperfused myocardial infarction (MI) were used to assess their myocardial regenerative capability "in vitro" and their effect on postinfarction left ventricular (LV) remodeling. Human BMCs were labeled, seeded on top of cryoinjured mice heart slices, and cultured. BMCs showed tropism for and ability to graft into the damaged mouse cardiac tissue and, after 1 week, acquired a cardiomyocyte phenotype and expressed cardiac proteins, including connexin43. In the clinical trial, autologous BMCs (78Ϯ41ϫ10 6 per patient) were intracoronarily transplanted 13.5Ϯ5.5 days after MI. There were no adverse effects on microvascular function or myocardial injury. No major cardiac events occurred up to 11Ϯ5 months. At 6 months, magnetic resonance showed a decrease in the end-systolic volume, improvement of regional and global LV function, and increased thickness of the infarcted wall, whereas coronary restenosis was only 15%. No changes were found in a nonrandomized contemporary control group. Thus, BMCs are capable of nesting into the damaged myocardium and acquire a cardiac cell phenotype in vitro as well as safely benefiting ventricular remodeling in vivo. Large-scale randomized trials are needed now to assess the clinical efficacy of this treatment.

show abstract

Section: Discussionsupporting

confidence: 85%

Experimental and Clinical Regenerative Capability of Human Bone Marrow Cells After Myocardial Infarction

Fernández‐Avilés

Román

García-Frade

et al. 2004

Circulation Research

430

193

View full text Add to dashboard Cite

show abstract

“…Similarly, oxygen diffusion from the blood in the left ventricular chamber to the endomyocardium can preserve progenitor cells in the ischemic region. Alternatively, CSCs can migrate from the surviving myocardium to the infarct and differentiate into myocytes and coronary vessels (5,26).…”

Section: Discussionmentioning

confidence: 99%

Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure

Urbanek

Torella

Sheikh

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

559

449

View full text Add to dashboard Cite

In this study, we tested whether the human heart possesses a cardiac stem cell (CSC) pool that promotes regeneration after infarction. For this purpose, CSC growth and senescence were measured in 20 hearts with acute infarcts, 20 hearts with end-stage postinfarction cardiomyopathy, and 12 control hearts. CSC number increased markedly in acute and, to a lesser extent, in chronic infarcts. CSC growth correlated with the increase in telomerasecompetent dividing CSCs from 1.5% in controls to 28% in acute infarcts and 14% in chronic infarcts. The CSC mitotic index increased 29-fold in acute and 14-fold in chronic infarcts. CSCs committed to the myocyte, smooth muscle, and endothelial cell lineages increased Ϸ85-fold in acute infarcts and Ϸ25-fold in chronic infarcts. However, p16 INK4a -p53-positive senescent CSCs also increased and were 10%, 18%, and 40% in controls, acute infarcts, and chronic infarcts, respectively. Old CSCs had short telomeres and apoptosis involved 0.3%, 3.8%, and 9.6% of CSCs in controls, acute infarcts, and chronic infarcts, respectively. These variables reduced the number of functionally competent CSCs from Ϸ26,000͞cm 3 of viable myocardium in acute to Ϸ7,000͞cm 3 in chronic infarcts, respectively. In seven acute infarcts, foci of spontaneous myocardial regeneration that did not involve cell fusion were identified. In conclusion, the human heart possesses a CSC compartment, and CSC activation occurs in response to ischemic injury. The loss of functionally competent CSCs in chronic ischemic cardiomyopathy may underlie the progressive functional deterioration and the onset of terminal failure.cardiac progenitor cells ͉ human heart ͉ myocardial infarction M yocardial regeneration occurs in humans after ischemic injury (1, 2), and myocyte proliferation appears to be restricted to the viable myocardium adjacent to and remote from the infarct (2). The identification of cardiac stem cells (CSCs) in the adult heart (3-7) suggests that replicating myocytes may constitute a subpopulation of rapidly growing amplifying cells originated from more primitive cells. CSCs are distributed throughout the heart, raising the possibility that those located within the infarct or in its proximity could divide and differentiate reconstituting dead myocardium. If this hypothesis were the case, strategies may be developed to enhance myocardial growth promoting partial restoration of the infarct. This response would reduce infarct size, improve function, and decrease mortality. Myocardial regeneration within the infarct could have escaped earlier observations because the heart was not viewed as a self-renewing organ, and myocyte replacement was considered to be regulated by a subset of cells capable of a few rounds of doubling, located by necessity in the spared portion of the ventricle (2). Alternatively, the lack of myocardial regeneration might reflect CSC death within the infarct and͞or the inability of CSCs to migrate and reach the necrotic area. Thus far, no evidence has been presented that CSCs can reconstitute i...

show abstract

“…A subset of parenchymal cells expresses the molecular components mediating the entry and progression of these cells through the cell cycle, and karyokinesis and cytokinesis. The recognition that myocyte replication, hypertrophy, and death occur in the pathological heart has significantly enhanced our understanding of the dynamic nature of the myocardium and the critical role that these variables have in the preservation of cardiac performance or in the onset of ventricular dysfunction (22,25,27,34,326,327). Contrary to the general belief, the restricted regenerative capacity of the myocardium does not represent the initial causal event of impaired cardiac function.…”

Section: Exogenous Progenitor Cells and Cardiac Repairmentioning

confidence: 99%

“…The early studies on BMCs and cardiac repair were followed by numerous reports in which different types of BMCs and modalities of interventions were employed for the treatment of the damaged heart (24,26,34). These cells of bone marrow origin included several subsets making it difficult to dissect the impact that each cell type had on the function and structure of the diseased heart.…”

Section: Controversy On Bone Marrow Cell Transdifferentiation and mentioning

confidence: 99%

Cardiac Stem Cells and Mechanisms of Myocardial Regeneration

Leri

Kajstura²,

Anversa³

2005

Physiological Reviews

Self Cite

397

349

View full text Add to dashboard Cite

This review discusses current understanding of the role that endogenous and exogenous progenitor cells may have in the treatment of the diseased heart. In the last several years, a major effort has been made in an attempt to identify immature cells capable of differentiating into cell lineages different from the organ of origin to be employed for the regeneration of the damaged heart. Embryonic stem cells (ESCs) and bone marrow-derived cells (BMCs) have been extensively studied and characterized, and dramatic advances have been made in the clinical application of BMCs in heart failure of ischemic and nonischemic origin. However, a controversy exists concerning the ability of BMCs to acquire cardiac cell lineages and reconstitute the myocardium lost after infarction. The recognition that the adult heart possesses a stem cell compartment that can regenerate myocytes and coronary vessels has raised the unique possibility to rebuild dead myocardium after infarction, to repopulate the hypertrophic decompensated heart with new better functioning myocytes and vascular structures, and, perhaps, to reverse ventricular dilation and wall thinning. Cardiac stem cells may become the most important cell for cardiac repair.

show abstract

Molecular Genetic Advances in Cardiovascular Medicine

Cited by 62 publications

References 41 publications

Experimental and Clinical Regenerative Capability of Human Bone Marrow Cells After Myocardial Infarction

Experimental and Clinical Regenerative Capability of Human Bone Marrow Cells After Myocardial Infarction

Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure

Cardiac Stem Cells and Mechanisms of Myocardial Regeneration

Contact Info

Product

Resources

About