Short‐ and long‐term outcomes of intracoronary and endogenously mobilized bone marrow stem cells in the treatment of ST‐segment elevation myocardial infarction: a meta‐analysis of randomized control trials

Abstract

AimsBone marrow stem cell (BMSC) treatment of ST-segment elevation myocardial infarction (STEMI) has been primarily via the intracoronary route or via endogenous mobilization using granulocyte colony-stimulating factor (G-CSF). Studies have provided conflicting results. We therefore performed a meta-analysis of these treatments, examining short-and long-term efficacy and safety. Methods and resultsRandomized controlled trials (RCTs) of BMSC-based therapy for STEMI, delivered within 9 days of reperfusion, were identified by systematic search. Random effects models were used to calculate pooled effects of clinical outcomes, with meta-regression to assess dependence of the magnitude of effect sizes on study characteristics. Twenty-nine RCTs enrolling 1830 patients were included. Intracoronary BMSC therapy resulted in an overall improvement in left ventricular ejection fraction (LVEF) of 2.70% [95% confidence interval (CI) 1.48-3.92; P , 0.001] in the short term and 3.31% (95% CI 1.87 -4.75; P , 0.001) longer term. Meta-regression suggested a dose-response relationship between quantity of CD34 + cells delivered and increase in LVEF (P ¼ 0.007). G-CSF treatment resulted in a trend towards similar benefits (P ¼ 0.20). No significant differences were observed in pooled adverse outcome rates between intervention and control groups of either treatment approach, except for lower revascularization rates with intracoronary BMSC vs. control (odds ratio 0.68, 95% CI 0.47-0.97; P ¼ 0.03). ConclusionsIntracoronary BMSC therapy post-STEMI improves LVEF beyond standard medical treatment, in both the short and longer term. G-CSF treatment shows positive but non-significant trends. Both treatments demonstrate safety comparable with conventional medical treatment.--

Heparin Disrupts the CXCR4/SDF-1 Axis and Impairs the Functional Capacity of Bone Marrow–Derived Mononuclear Cells Used for Cardiovascular Repair

“…The findings in tumor-bearing mice suggest that systemically administered heparin indeed effectively blocks CXCR4 signaling, 25,26 and one may speculate that the use of heparin might have limited the effects of strategies to augment endogenous stem cell mobilization, eg, by granulocyte-colony-stimulating factor. 4 Further studies are warranted to determine whether heparin may interfere with homing of applied or endogenously mobilized cells to the injured myocardium. Importantly, because the effects of heparin can be ameliorated by excessive serum in vitro (data not shown), the concentration of heparin in relation to serum should be taken into consideration.…”

Quality Control for Mesenchymal Stromal Cells: Chondrogenesis as a Standard Condition?

“…With the first attempts to introduce MSCs in regenerative treatment patterns, perhaps most spectacularly in heart diseases [19,20], the issue of uniform standardization has gained more and more attention. Oversight agencies have drafted legal frameworks and definitions (TEMP = tissue engineered medicinal products (USA), ATMP = advanced therapies medicinal products (EU)) but their conversion into measurable methodology still remains to be implemented.…”

Pathophysiological aspects and management workflow of coronary microvascular obstruction in ST-segment elevation myocardial infarction

“…82 The utility of stem cells in CMVO has provided mixed results. 77,83 Indeed, improvement of CFR after cell therapy has not consistently been shown in all trials, 83 conversely in the presence of CMVO, the improvement of LVEF associated with stem cell treatment seems to be dampened. 77 In a recent study, the addition of cilostazol (for 1 month) to double antiplatelet therapy with aspirin and clopidogrel in patients with angiographic CMVO improved the clinical outcome after 1 year.…”