Intracoronary Bone Marrow Cell Transfer After Myocardial Infarction Eighteen Months’ Follow-Up Data From the Randomized, Controlled BOOST (BOne marrOw transfer to enhance ST-elevation infarct regeneration) Trial

Department of Cardiology and Angiology , Hannover Medical School, Hanover, Lower Saxony, Germany
Circulation (Impact Factor: 14.43). 04/2006; 113(10):1287-94. DOI: 10.1161/CIRCULATIONAHA.105.575118
Source: PubMed


Intracoronary transfer of autologous bone marrow cells (BMCs) may enhance recovery of left ventricular (LV) function in patients after acute myocardial infarction (AMI). However, clinical studies addressing the effects of BMCs after AMI have covered only limited time frames ranging from 3 to 6 months. The critical question of whether BMC transfer can have a sustained impact on LV function remains unanswered.
After percutaneous coronary intervention with stent implantation (PCI) of the infarct-related artery, 60 patients were randomized 1:1 to a control group with optimal postinfarction therapy and a BMC transfer group that also received an intracoronary BMC infusion 4.8+/-1.3 days after PCI. Cardiac MRI was performed 3.5+/-1.5 days, 6+/-1 months, and 18+/-6 months after PCI. BMC transfer was not associated with adverse clinical events. In the control group, mean global LV ejection fraction increased by 0.7 and 3.1 percentage points after 6 and 18 months, respectively. LV ejection fraction in the BMC transfer group increased by 6.7 and 5.9 percentage points. The difference in LVEF improvement between groups was significant after 6 months but not after 18 months (P=0.27). The speed of LV ejection fraction recovery over the course of 18 months was significantly higher in the BMC transfer group (P=0.001).
In this study, a single dose of intracoronary BMCs did not provide long-term benefit on LV systolic function after AMI compared with a randomized control group; however, the study suggests an acceleration of LV ejection fraction recovery after AMI by BMC therapy.

Download full-text


Available from: Stephanie Fichtner, Aug 02, 2015
  • Source
    • "marrow in cases of cardiac injury . Optimistic results have been reported , such as an acceleration of left ven - tricular ejection fraction ( LVEF ) recovery after acute myocardial infarction , although this was observed without a long - term ben - efit on left ventricular systolic function measured at 18 months after bone marrow cells transfer ( Meyer et al . , 2006 ) . However , a trend in favor of this cell therapy is defended , particularly consid - ering patients with severely impaired LVEF at baseline ( Tendera et al . , 2009 ) . The favorable results arising from the transplan - tation of bone marrow cells have been attributed to humoral ( Cho et al . , 2007 ) and paracrine effects rather tha"
    [Show abstract] [Hide abstract]
    ABSTRACT: The last decade has brought a comprehensive change in our view of cardiac remodeling processes under both physiological and pathological conditions, and cardiac stem cells have become important new players in the general mainframe of cardiac homeostasis. Different types of cardiac stem cells show different capacities for differentiation into the three major cardiac lineages: myocytes, endothelial cells and smooth muscle cells. Physiologically, cardiac stem cells appear to contribute to cardiac homeostasis through continual cellular turnover. Pathologically, these cells exhibited a high level of proliferative activity in an apparent attempt to repair acute cardiac injury, indicating that these cells have regenerative potential, albeit limited. In addition to these cardiac stem cells, mesenchymal stem cells represent another multipotent cellular population in the heart that are located in regions near pericytes and exhibit regenerative, angiogenic, antiapoptotic, and immunosuppressive properties. The discovery of these resident cardiac stem cells was followed by a number of experimental studies in animal models of cardiomyopathies, in which cardiac stem cells were tested as a therapeutic option to overcome the limited transdifferentiating potential of hematopoietic or mesenchymal stem cells derived from bone marrow. The promising results of these studies prompted clinical studies of the role of these cells, which have demonstrated the safety and practicability of cellular therapies for the treatment of heart disease. However, questions remain. The aim of the present review was to discuss the multitude of different cardiac stem cells that have been identified, their possible functional roles in the cardiac regenerative process, and their potential therapeutic uses in treating cardiac diseases.
    Frontiers in Physiology 05/2015; Front. Physiol.(6). DOI:10.3389/fphys.2015.00123 · 3.53 Impact Factor
  • Source
    • "The latter finding was attributed to a “catch-up” phenomenon in ventricular function of placebo treated patients. Interestingly, similar “catch-up” has been reported in BMMNC therapy trials (Meyer et al. 2006). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Following significant injury, the heart undergoes induced compensation and gradually deteriorates towards impending heart failure. Current therapy slows but does not halt the resultant adverse remodeling. Stem cell therapy, however, has the potential to regenerate or repair infarcted heart tissue and therefore is a promising therapeutic strategy undergoing intensive investigation. Due to the wide range of stem cells investigated, it is difficult to navigate this field. This review aims to summarize the main types of stem cells (both of cardiac and extra-cardiac origin) that possess promising therapeutic potential. Particular focus is placed on clinical trials supporting this therapeutic strategy.
    SpringerPlus 08/2014; 3(1):440. DOI:10.1186/2193-1801-3-440
  • Source
    • "Intracoronary delivery of bone marrow-derived mononuclear cells by the “stop-flow technique” after acute STEMI has proven to be safe and is associated with modest improvement in LVEF [6–8, 10, 13, 15–17, 20–23, 25, 29, 30, 39, 46–48]. Meta-analyses suggest that the benefit of cell therapy on postinfarct cardiac function is only apparent if cells are infused during the repair phase after STEMI, given in sufficient quantity, and with adequate mobility in an SDF-1 gradient [29, 31, 47]; however, a major limitation has been the heterogeneity of unselected bone marrow mononuclear cells and the variability in cell doses employed. The CD34 surface marker identifies a population of cells within the bone marrow that exhibit regenerative characteristics, but only one study (in addition to our own) has examined the utility of CD34+ cell therapy, but at a relatively low cell dose [25, 49]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: ST elevation myocardial infarction (STEMI) is associated with an increased risk for congestive heart failure and long-term mortality despite the widespread use of thrombolysis and catheter-based revascularization. The need for improved post-STEMI therapies has led to a surge of novel therapeutics, especially regenerative approaches using autologous mononuclear cells. Indeed, the past decade has been marked by a number of human trials studying the safety and efficacy of progenitor cell delivery in the post-STEMI setting. While a variety of cell types and delivery techniques have been utilized, directed therapy to the infarct-related artery has been the most widely used approach. From over 1300 subjects randomized in these studies, there is sufficient evidence to conclude that cell therapy after STEMI is uniformly safe, while the efficacy of this intervention for improving outcomes is less clear. Recent meta-analyses have highlighted the importance of both timing of cell delivery, as well as the type, quantity, and mobility of delivered cells as determinants of response. Here, we show the case in which higher doses of CD34(+) cells, which are more potent in terms of their migratory capacity, offer the best hope for preserving cardiac function following STEMI.
    Stem cell International 04/2013; 2013:658480. DOI:10.1155/2013/658480 · 2.81 Impact Factor
Show more