Transcoronary Transplantation of Progenitor Cells after Myocardial Infarction

Aßmus, Birgit; Honold, Jörg; Schächinger, Volker; Britten, Martina; Fischer‐Rasokat, Ulrich; Lehmann, Ralf; Teupe, Claudius; Pistorius, K.; Martin, Hans; Abolmaali, Nasreddin; Tonn, Torsten; Dimmeler, Stefanie; Zeiher, Andreas M.

doi:10.1056/nejmoa051779

Cited by 972 publications

(663 citation statements)

References 22 publications

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“…For example, the MAGIC II trial of skeletal myoblast transplantation into chronic infarcts was terminated early by the study's data safety monitoring board, because the treatment offered no benefit on ejection fraction compared to placebo [29]. Similarly, delivery of bone marrow cells to patients with acute MI has produced mixed results, with two negative trials [30,31], one showing transient benefit [32] and one showing sustained benefit [33]. The reasons for this failure to translate preclinical results into benefits in humans are not known, but a good candidate is the vast difference in cell number required for human therapy compared to rodents.…”

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

361

294

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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.

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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

361

294

View full text Add to dashboard Cite

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“…43,53,54,62 Heart Failure Additionally, there have been multiple HF trials (Table 2). Many demonstrated benefits in ventricular function noted by increased EF, [68][69][70][71][72][73]75,79,82,83 improved functional class, 75,78,80,82,83,86 reduced infarct size, 70,72,80,[82][83][84] decreased mortality, 79 and acceptable safety outcomes. [66][67][68][69]75,78,80,[82][83][84]86 SCIPIO was the first trial using autologous CSC in HF and showed improvement in EF, infarct size, viable tissue, and HF scores.…”

Section: Clinical Outcomes Acute Myocardial Infarctionmentioning

confidence: 99%

Stem Cell Therapy for Heart Disease

2013

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Coronary artery disease is the leading cause of death in Americans. After myocardial infarction, significant ventricular damage persists despite timely reperfusion and pharmacological management. Treatment is limited, as current modalities do not cure this damage. In the past decade, stem cell therapy has emerged as a promising therapeutic solution to restore myocardial function. Clinical trials have demonstrated safety and beneficial effects in patients suffering from acute myocardial infarction, heart failure, and dilated cardiomyopathy. These benefits include improved ventricular function, increased ejection fraction, and decreased infarct size. Mechanisms of therapy are still not clearly understood. However, it is believed that paracrine factors, including stromal cell-derived factor-1, contribute significantly to stem cell benefits. The purpose of this article is to provide medical professionals with an overview on stem cell therapy for the heart and to discuss potential future directions.

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“…Patients were derived from 2 study cohorts with the same inclusion criteria. 15,16 The ethics committee of the J.W. Goethe University reviewed and approved the study protocols.…”

Section: Patient Populationmentioning

confidence: 99%

Comparison of the Seattle Heart Failure Model and Cardiopulmonary Exercise Capacity for Prediction of Death in Patients With Chronic Ischemic Heart Failure and Intracoronary Progenitor Cell Application

Honold

Rosa

Spyridopoulos

et al. 2013

Clinical Cardiology

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Background: Despite many therapeutic advances, the prognosis of patients with chronic heart failure (CHF) remains poor. Therefore, reliable identification of high-risk patients with poor prognosis is of utmost importance. Cardiopulmonary exercise testing (CPET) provides important prognostic information by peak O 2 uptake (peak VO 2 ), maximal oxygen pulse (O 2 Pmax), O 2 uptake efficiency slope (OUES), and VE/VCO 2 slope (VE/VCO 2 ). A different approach for prognostic assessment is the Seattle Heart Failure Model (SHFM), which is based on clinical data and calculates the estimated annual mortality. Hypothesis: Comparison of the prognostic value of the Seattle Heart Failure Score and cardiopulmonary excercis testing in patients with chronic heart failure. Methods: One hundred fifty-seven patients with ischemic heart failure and recent intracoronary progenitor cell application were analyzed for mortality during a follow-up of 4 years. CPET (peak VO 2 , O 2 Pmax, OUES, VE/VCO 2 ) was performed in all patients at baseline. The SHFM score was calculated for every patient, with data obtained at the time of CPET. Results: During follow-up, 24 patients died (15.2%). Nonsurvivors had significantly worse initial CPET results and a higher SHFM score compared to survivors. Receiver operating characteristics curve analysis of sensitivity and specificity revealed the largest area under the curve value for the SHFM score, followed by VE/VCO 2 slope. Kaplan Meier analysis using cutoff points of SHFM and VE/VCO 2 slope with highest sensitivity and specificity resulted in significant discrimination of survivors and nonsurvivors. By multivariate analysis, only the SHFM score persisted as independent predictor of mortality in these patients. Conclusions: These data indicate superior prognostic power of the SHFM score compared to CPET in patients with chronic ischemic heart failure. IntroductionHeart failure is associated with high mortality rates, prolonged and repeated hospitalizations, and enormous implications for healthcare systems. Despite novel therapeutic options like revascularization, device therapy, and pharmacotherapy, the prevalence and incidence of chronic heart failure continued to increase over the last decades. 1 The identification of high-risk patients requires objective assessment of mortality risk. Cardiopulmonary exercise

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Transcoronary Transplantation of Progenitor Cells after Myocardial Infarction

Abstract: Intracoronary infusion of progenitor cells is safe and feasible in patients with healed myocardial infarction. Transplantation of BMC is associated with moderate but significant improvement in the left ventricular ejection fraction after 3 months.

Cited by 972 publications

References 22 publications

Systems approaches to preventing transplanted cell death in cardiac repair

Systems approaches to preventing transplanted cell death in cardiac repair

Stem Cell Therapy for Heart Disease

Comparison of the Seattle Heart Failure Model and Cardiopulmonary Exercise Capacity for Prediction of Death in Patients With Chronic Ischemic Heart Failure and Intracoronary Progenitor Cell Application

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