Intramyocardial delivery of purified bone marrow stem cells together with CABG surgery is safe and provides beneficial effects, though it remains to be seen whether thewe effects produce a lasting clinical advantage.

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Our meta-analysis provides evidence that preoperative statin therapy exerts substantial clinical benefit on early postoperative adverse outcomes in cardiac surgery patients, but underscores the need for RCT trials.

BackgroundDuring the last decade, mesenchymal stem cells (MSCs) have gained much attention in the field of regenerative medicine due to their capacity to differentiate into different cell types and to promote immunosuppressive effects. However, the underlying mechanism of MSC-mediated immunoregulation is not fully understood so far. Macrophages are distinguished in classical activated, pro-inflammatory M1 and alternatively activated M2 cells, which possess different functions and transcriptional profiles with respect to inflammatory responses. As polarization is not fixed, macrophage functional plasticity might be modulated by the microenvironment allowing them to rapidly react to danger signals and maintaining tissue homeostasis.MethodsMurine MSCs were preconditioned with IL-1ß and IFN-ɣ to enhance their immunosuppressive capacity regarding macrophage polarization under M1- and M2a-polarizing conditions. Macrophage polarization was analyzed by real-time PCR, flow cytometry, and cytokine detection in culture supernatants. The role of MSC-derived nitric oxide (NO), prostaglandin E2 (PGE2), and IL-6 in this process has been evaluated using siRNA transfection and IL-6 receptor-deficient macrophages, respectively.ResultsPreconditioned, but not unprimed, MSCs secreted high levels of NO, IL-6, and PGE2. Co-culture with macrophages (M0) in the presence of M1 inducers (LPS + IFN-ɣ) led to significant reduction of CD86 and iNOS protein in macrophages and diminished TNF-α secretion. Additionally, CD86 and iNOS protein expression as well as NO and IL-10 secretion were markedly increased under M2a-polarizing culture conditions (IL-4). MSC-dependent macrophage polarization did not depend on direct cell-cell contact. Co-culturing in the presence of LPS and IFN-ɣ resulted in the upregulation of M2a, M2b, and M2c marker genes, whereas in the presence of IL-4 only M2b markers were significantly increased. In turn, IL-10-producing regulatory M2b cells significantly inhibited IFN-ɣ expression in CD4+ T lymphocytes. Finally, we show that MSC-mediated macrophage polarization strongly depends on IL-6, whereas a minor role for NO and PGE2 was found.ConclusionsPreconditioning of MSCs highly strengthens their capacity to regulate macrophage features and to promote immunosuppression. Repression of M1 polarization during inflammation and M2b polarization under anti-inflammatory conditions strongly depend on functional IL-6 signaling in macrophages. The potential benefit of preconditioned MSCs and IL-6 should be considered for future clinical treatment.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-1039-2) contains supplementary material, which is available to authorized users.

Ventricular hypertrophy is an ominous escalation of hemodynamically stressful conditions such as hypertension and valve disease. The pathophysiology of hypertrophy is complex and multifactorial, as it touches on several cellular and molecular systems. Understanding the molecular background of cardiac hypertrophy is essential in order to protect the myocardium from pathological remodeling, or slow down the destined progression to heart failure. In this review we highlight the most important molecular aspects of cardiac hypertrophic growth in light of the currently available published research data.

In the present systematic review with meta-analysis, we sought to determine the current strength of evidence for or against off-pump and on-pump coronary artery bypass grafting (CABG) with regard to hard clinical end-points, graft patency and cost-effectiveness. We performed a meta-analysis of only randomized controlled trials (RCT) which reported at least one of the desired end-points including: (i) major adverse cardiac and cerebrovascular events (MACCE), (ii) all-cause mortality, (iii) myocardial infarction, (iv) cerebrovascular accident, (v) repeat revascularization, (vi) graft patency and (vii) cost-effectiveness. The pooled treatment effects [odds ratio (OR) or weighted mean difference, 95% confidence intervals (95% CIs)] were assessed using a fixed or random effects model. A total of 16 904 patients from 51 studies were identified after literature search of the major databases using a predefined keyword list. The incidence of MACCE did not differ between the groups, neither during the first 30 days (OR: 0.93; 95% CI: 0.82-1.04) nor for the longest available follow-up (OR: 1.01; 95% CI: 0.92-1.12). While the incidence of mid-term graft failure (OR: 1.37; 95% CI: 1.09-1.72) and the need for repeat revascularization (OR: 1.55; 95% CI: 1.33-1.80) was increased after off-pump surgery, on-pump surgery was associated with an increased occurrence of stroke (OR: 0.74; 95% CI: 0.58-0.95), renal impairment (OR: 0.79; 95% CI: 0.71-0.89) and mediastinitis (OR: 0.44; 95% CI: 0.31-0.62). There was no difference with regard to hard clinical end-points between on- or off-pump surgery, including myocardial infarction or mortality. The present systematic review emphasizes that both off- and on-pump surgery provide excellent and comparable results in patients requiring surgical revascularization. The choice for either strategy should take into account the individual patient profile (comorbidities, life expectancy, etc.) and importantly, the surgeon's experience in performing on- or off-pump CABG in their routine practice.

Extracellular matrix (ECM) derived by tissue decellularization has applications as a tissue engineering scaffold and for support of cellular regeneration. Myocardial ECM from animals has been produced by whole-organ perfusion or immersion processes, but methods for preparation of human myocardial ECM for therapy and research have not been compared in detail, yet. We analyzed the impact of decellularization processes on human myocardial ECM, and tested its ability to serve as a scaffold for cell seeding. Sodium dodecyl sulfate (SDS)-based decellularization, but not treatments based on Triton X-100, deoxycholate or hypo/hypertonic incubations, removed cells satisfactorily, and incubation with fetal bovine serum (FBS) eliminated residual DNA. ECM architecture was best preserved by a protocol consisting of 2 h lysis, 6 h SDS, and 3 h FBS, but age and pathology of the donor tissue are highly important for producing reproducible, high-quality scaffolds. We also studied ECM repopulation with mesenchymal stem cells (CB-MSC), cardiomyocytes derived from induced pluripotent stem cells (iPS-CM), and na€ıve neonatal mouse cardiomyocytes. Cells attached to the matrix and proliferated and displayed higher viability than in standard culture. We conclude that human cardiac ECM sheets may be suitable scaffold for cell-matrix interaction studies and as a biomaterial for tissue regeneration and engineering.

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