Cell-Based Cardiac Repair

Murry, Charles E.; Field, Loren J.; Menasché, Philippe

doi:10.1161/circulationaha.105.546218

Cited by 325 publications

(96 citation statements)

References 105 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Importantly, clonogenic hCSCs have the inherent potential to form contracting myocardium integrated structurally and functionally with the recipient heart. Although CSCs with similar characteristics were shown in animal models (4,5), the applicability of this information to humans was seriously questioned and considered a major limitation for the clinical implementation of CSCs (15).…”

Section: Discussionmentioning

confidence: 99%

Human cardiac stem cells

Bearzi

Rota

Hosoda

et al. 2007

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

917

896

View full text Add to dashboard Cite

The identification of cardiac progenitor cells in mammals raises the possibility that the human heart contains a population of stem cells capable of generating cardiomyocytes and coronary vessels. The characterization of human cardiac stem cells (hCSCs) would have important clinical implications for the management of the failing heart. We have established the conditions for the isolation and expansion of c-kit-positive hCSCs from small samples of myocardium. Additionally, we have tested whether these cells have the ability to form functionally competent human myocardium after infarction in immunocompromised animals. Here, we report the identification in vitro of a class of human c-kit-positive cardiac cells that possess the fundamental properties of stem cells: they are self-renewing, clonogenic, and multipotent. hCSCs differentiate predominantly into cardiomyocytes and, to a lesser extent, into smooth muscle cells and endothelial cells. When locally injected in the infarcted myocardium of immunodeficient mice and immunosuppressed rats, hCSCs generate a chimeric heart, which contains human myocardium composed of myocytes, coronary resistance arterioles, and capillaries. The human myocardium is structurally and functionally integrated with the rodent myocardium and contributes to the performance of the infarcted heart. Differentiated human cardiac cells possess only one set of human sex chromosomes excluding cell fusion. The lack of cell fusion was confirmed by the Cre-lox strategy. Thus, hCSCs can be isolated and expanded in vitro for subsequent autologous regeneration of dead myocardium in patients affected by heart failure of ischemic and nonischemic origin.generation of human myocardium ͉ progenitor cells ͉ stem cell niches

show abstract

Section: Discussionmentioning

confidence: 99%

Human cardiac stem cells

Bearzi

Rota

Hosoda

et al. 2007

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

917

896

View full text Add to dashboard Cite

show abstract

“…Many strategies being pursued to restore heart function involve repopulating the heart with exogenously delivered cells, either by direct injection [1,2] or intravascular delivery. The first attempts to repopulate the scarred aftermath of myocardial infarction (MI) were performed over fifteen years ago [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Systems approaches to preventing transplanted cell death in cardiac repair

Robey

Saiget

Reinecke

et al. 2008

Journal of Molecular and Cellular Cardiology

Self Cite

364

294

View full text Add to dashboard Cite

Stem cell transplantation may repair the injured heart, but tissue regeneration is limited by death of transplanted cells. Most cell death occurs in the first few days post-transplantation, likely from a combination of ischemia, anoikis and inflammation. Interventions known to enhance transplanted cell survival include heat shock, over-expressing anti-apoptotic proteins, free radical scavengers, anti-inflammatory therapy and co-delivery of extracellular matrix molecules. Combinatorial use of such interventions markedly enhances graft cell survival, but death still remains a significant problem. We review these challenges to cardiac cell transplantation and present an approach to systematically address them.Most anti-death studies use histology to assess engraftment, which is time-and labor-intensive. To increase throughput, we developed two biochemical approaches to follow graft viability in the mouse heart. The first relies on LacZ enyzmatic activity to track genetically modified cells, and the second quantifies human genomic DNA content using repetitive Alu sequences. Both show linear relationships between input cell number and biochemical signal, but require correction for the time lag between cell death and loss of signal. Once optimized, they permit detection of as few as 1 graft cell in 40,000 host cells. Pro-survival effects measured biochemically at three days predict long-term histological engraftment benefits. These methods permitted identification of carbamylated erythropoietin (CEPO) as a pro-survival factor for human embryonic stem cell-derived cardiomyocyte grafts. CEPO's effects were additive to heat shock, implying independent survival pathways. This system should permit combinatorial approaches to enhance graft viability in a fraction of the time required for conventional histology.

show abstract

“…The putative role of CSC in the heart's ability to withstand imposed wear and tear is exciting but actively debated. This is because a myocardial infarction results in the loss of tens of millions of cells, and this might be too great to be repaired through the cell division of the few cardiac progenitors [10,11]. Notably, even the proponents of CSC find that these cells give rise only to smaller mononucleated myocytes that phenotypically resemble both neonatal cardiomyocytes or embryonic stem cells during the early stages of their differentiation into cardiac lineage [12].…”

Section: Cell Sources For Cardiac Transplantation Cardiac Stem Cells mentioning

confidence: 99%

“…While these findings might appear too good to be true, if confirmed by subsequent studies, they offer an enormous promise because they suggest that the adult heart possesses true multipotent CSC. On a cautious side, it is important to note that the validity of the markers, such as Sca1, c-kit, isl+, to adequately identify CSC is questionable [11]. There is also a concern regarding the minute amount and mitotic capacity of these cells, which may limit the ability of endogenous CSC to make a difference in cardiac muscle repair [10,15].…”

Section: Cell Sources For Cardiac Transplantation Cardiac Stem Cells mentioning

confidence: 99%

Adhesion Proteins, Stem Cells, and Arrhythmogenesis

Gillum

Sarvazyan

2008

Cardiovasc Toxicol

View full text Add to dashboard Cite

Cell-transplantation therapy is a promising treatment option that is being actively explored as a way to repair cardiac muscle. The ultimate goal is to reconstitute the architecture of the cardiac muscle and to reestablish electrical propagation, while avoiding hypertrophy and scar formation. In this review, we focus on recent advances in the field as well as the difficulties encountered when the engraftment of cells into the host tissue is to be confirmed and functionally characterized. This is critical since incomplete or partial engraftment of transplanted cells within the host cardiac network exacerbates the heterogeneity already present in the injured myocardium and increases its propensity to arrhythmia. We conclude with a brief discussion of how the modulation of cell adhesion via modification of coupling proteins within transplanted cells may facilitate engraftment and alleviate the arrhythmogenic potential of cardiac grafts.

show abstract

Cell-Based Cardiac Repair

Cited by 325 publications

References 105 publications

Human cardiac stem cells

Human cardiac stem cells

Systems approaches to preventing transplanted cell death in cardiac repair

Adhesion Proteins, Stem Cells, and Arrhythmogenesis

Contact Info

Product

Resources

About