Microvesicles (MVs) are membrane-enclosed cytoplasmic fragments released by normal and activated cells that have been described as important mediators of cell-to-cell communication.Although the ability of human induced pluripotent stem cells (hiPSCs) to participate in tissue repair is being increasingly recognized, the use of hiPSC-derived MVs (hiPSC-MVs) in this regard remains unknown. Accordingly, we investigated the ability of hiPSC-MVs to transfer bioactive molecules including mRNA, microRNA (miRNA), and proteins to mature target cells such as cardiac mesenchymal stromal cells (cMSCs), and we next analyzed effects of hiPSC-MVs on fate and behavior of such target cells. The results show that hiPSC-MVs derived from integration-free hiPSCs cultured under serum-free and feeder-free conditions are rich in mRNA, miRNA, and proteins originated from parent cells; however, the levels of expression vary between donor cells and MVs. Importantly, we found that transfer of hiPSC components by hiPSC-MVs impacted on transcriptome and proteomic profiles of target cells as well as exerted proliferative and protective effects on cMSCs, and enhanced their cardiac and endothelial differentiation potential. hiPSC-MVs also transferred exogenous transcripts from genetically modified hiPSCs that opens new perspectives for future strategies to enhance MV content. We conclude that hiPSC-MVs are effective vehicles for transferring iPSC attributes to adult somatic cells, and hiPSC-MV-mediated horizontal transfer of RNAs and proteins to injured tissues may be used for therapeutic tissue repair. In this study, for the first time, we propose a new concept of use of hiPSCs as a source of safe acellular bioactive derivatives for tissue regeneration. STEM CELLS 2015;33:2748-2761 SIGNIFICANCE STATEMENTOur results show, for the first time, that human induced pluripotent stem cells (hiPS cells) may serve as a source of bioactive microvesicles (MVs) that could be potentially utilized for future safe applications in tissue regeneration. For the first time, we extensively characterized bioactive content of MVs released by hiPS cells (hiPS-MVs) on both transcriptomic and proteomic levels and we established their impact on functions and differentiation potential of mature target cells from human heart. These results have obvious translational relevance for developing potential new iPS cell-based strategies in tissue regeneration by employing thier safe acellular bioactive derivatives.

A stable haemodynamic status due to independent coronary perfusion, higher diastolic and lower pulse pressure is the most advantageous effect of RV-PA, resulting in a lower mortality and morbidity after NP. A lower Qp:Qs ratio eliminates the danger of the ventricular volume overload and ensures good conditions for the development of the pulmonary circulation before HF.

Growing evidence indicates that intracellular signaling mediated by extracellular vesicles (EVs) released by stem cells plays a considerable role in triggering the regenerative program upon transplantation. EVs from umbilical cord mesenchymal stem cells (UC-MSC-EVs) have been shown to enhance tissue repair in animal models. However, translating such results into clinical practice requires optimized EV collection procedures devoid of animal-originating agents. Thus, in this study, we analyzed the influence of xeno-free expansion media on biological properties of UC-MSCs and UC-MSC-EVs for future applications in cardiac repair in humans. Our results show that proliferation, differentiation, phenotype stability, and cytokine secretion by UC-MSCs vary depending on the type of xeno-free media. Importantly, we found distinct molecular and functional properties of xeno-free UC-MSC-EVs including enhanced cardiomyogenic and angiogenic potential impacting on target cells, which may be explained by elevated concentration of several pro-cardiogenic and pro-angiogenic microRNA (miRNAs) present in the EVs. Our data also suggest predominantly low immunogenic capacity of certain xeno-free UC-MSC-EVs reflected by their inhibitory effect on proliferation of immune cells in vitro. Summarizing, conscious selection of cell culture conditions is required to harvest UC-MSC-EVs with the optimal desired properties including enhanced cardiac and angiogenic capacity, suitable for tissue regeneration.Key message Type of xeno-free media influences biological properties of UC-MSCs in vitro.Certain xeno-free media promote proliferation and differentiation ability of UC-MSCs.EVs collected from xeno-free cultures of UC-MSCs are biologically active.Xeno-free UC-MSC-EVs enhance cardiac and angiogenic potential of target cells.Type of xeno-free media determines immunomodulatory effects mediated by UC-MSC-EVs. Electronic supplementary materialThe online version of this article (doi:10.1007/s00109-016-1471-7) contains supplementary material, which is available to authorized users.

Elective repair of TOF in neonates with confluent central pulmonary arteries has excellent results in the absence of significant associated non-cardiac conditions. While enhancing the development and growth of the pulmonary arteries, neonatal repair affords a freedom from reintervention no different from patients repaired during infancy. Preoperative weight < 2.5 kg and small left pulmonary artery size are associated with higher incidence reintervention during follow-up.

Combined poisoning with calcium-channel blockers and beta-blockers is usually associated with severe heart failure. This report shows the effectiveness of emergency extracorporeal life support in treating life-threatening simultaneous propranolol and verapamil intoxication. A 15-year-old girl presented in cardiogenic shock after alcohol consumption and a propranolol and verapamil overdose; plasma concentrations: propranolol, 0.53 m/mL; verapamil, 1.06 mg/mL. She was successfully resuscitated with extracorporeal life support. Therapeutic plasma exchange was initiated. Extracorporeal support was discontinued 70 hours later. The patient made a full recovery. Simultaneous verapamil and propranolol overdoses can cause severe hemodynamic compromise and arrest of electrical and mechanical function of the heart. Emergency extracorporeal life support can successfully maintain vital organ blood flow and allows time for drug metabolism, redistribution, and removal. Therapeutic plasma exchange may reduce the time of emergency extracorporeal life support. Emergency extracorporeal life support should be considered early in cases of near-fatal intoxications with cardiodepressive drugs.