AimsTo investigate the effect of survivin (SVV)-engineered mesenchymal stem cells (MSCs) on post-infarction cardiac performance and remodelling in rats. Methods and resultsMesenchymal stem cells from male Sprague-Dawley rat bone marrow were infected with the self-inactive lentiviral vector GFP-wre-CMV/LTR and Flap-Ubiqutin promoter (GCFU) carrying green fluorescent protein (GFP) gene and SVV recombinant vector (GCFU-SVV). In vitro, modification with SVV increased the secretion of vascular endothelial growth factor (VEGF) by 1.28-fold under hypoxic conditions. In vivo, after permanent left anterior descending artery occlusion, rats were randomized (n ¼ 18 per group) to receive intra-myocardial injections of 100 mL of phosphatebuffered saline without cells (group vehicle) or containing 2 million MSC GFP (group MSC GFP ) or MSC SVV (group MSC SVV ) cells. Cellular survival assessed by reverse transcriptase-polymerase chain reaction for GFP in the MSC SVV group was 2.5-fold higher at 7 days and 4.3-fold higher at 28 days after transplantation than in the MSC GFP group. When compared with transplantation with MSC GFP , transplantation with MSC SVV further upregulated VEGF expression at 7 and 28 days after myocardial infarction (MI), increased capillary density by 38%, reduced the infarct size by 12.7%, significantly inhibited collagen deposition, and further improved cardiac function at 28 days after MI. ConclusionTransplantation with SVV-engineered MSCs by lentiviral vector leads to better prognosis for MI by enhancing cellular survival.--

Stent grafting of the ascending aorta is technically feasible but should be reserved for selected high-risk patients only, preferably in centers where vascular specialists cooperate closely with interventional cardiologists. Cardiac surgery with cardiopulmonary bypass is still the gold standard to treat ascending aortic aneurysms. Stent graft exclusion of more advanced and complex ascending aortic pathology should be performed only in centers with the necessary experience in transvalvular cardiac procedures.

BackgroundThis study was performed to determine whether injury induced by cerebral ischemia could be further improved by transplantation with bone marrow-derived mesenchymal stem cells (MSCs) modified by Survivin (SVV).MethodsMSCs derived from bone marrow of male Sprague-Dawley rats were infected by the self-inactive lentiviral vector GCFU carrying green fluorescent protein (GFP) gene and SVV recombinant vector (GCFU-SVV). In vitro, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were detected in infected MSCs supernatants under hypoxic conditions by ELSIA. In vivo, experiments consisted of three groups, one receiving intravenous injection of 500 μl of phosphate-buffered saline (PBS) without cells (control group) and two groups administered the same volume solution with either three million GFP-MSCs (group GFP) or SVV/GFP-MSCs (group SVV). All animals were submitted to 2-hour middle cerebral artery occlusion (MCAO) and then reperfusion. Differentiation and survival of the transplanted MSCs were determined by confocal microscope. Western blot was used to detect the expression of VEGF and bFGF in ischemic tissue. A 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to assess the infarct volume. Evaluation of neurological function was performed using a modified Neurological Severity Score (mNSS).ResultsIn vitro, modification with SVV further increased secretion of VEGF and bFGF under hypoxic condition. In vivo, only very few transplantated cells co-expressed GFP and NeuN. The survival transplanted cells in the group SVV was 1.3-fold at 4 days after transplantation and 3.4-fold higher at 14 days after transplantation, respectively, when compared with group GFP. Expression of VEGF and bFGF in the ischemic tissue were further up-regulated by modification with SVV. Moreover, modification with SVV further reduced the cerebral infarct volume by 5.2% at 4 days after stroke and improved post-stroke neurological function at 14 days after transplantation.ConclusionModification with SVV could further enhance the therapeutic effects of MSCs possibly through improving the MSCs survival capacity and up-regulating the expression of protective cytokines in the ischemic tissue.

Failure of beta-cell function might be the main reason for both IGT and IFG developing into diabetes instead of aggravated insulin resistance.

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For STEMI patients with HTB who have undergone initial thrombectomy, delayed stenting is safe and feasible, and may be associated with better immediate myocardial perfusion, more LV function recovery, and less occurrence of MACE at the 1-year follow-up.

RSV pretreatment was associated with more Treg accumulation, less inflammatory response, and myocardial injury, suggesting that such cardioprotection against IRI was partially mediated by Treg-negative modulation of inflammation response, probably through the HMG-CoA reductase pathway.

Aims/hypothesis Dysregulation of biochemical pathways in response to hyperglycaemia in cells intrinsic to the nervous system (Schwann cells, neurons, vasa nervorum) are thought to underlie diabetic peripheral neuropathy (DPN). TNF-α is a known aetiological factor; Tnf-knockout mice are protected against DPN. We hypothesised that TNF-α produced by a small but specific bone marrow (BM) subpopulation marked by proinsulin production (proinsulin-producing BM-derived cells, PI-BMDCs) is essential for DPN development. Methods We produced mice deficient in TNF-α, globally in BM and selectively in PI-BMDCs only, by gene targeting and BM transplantation, and induced diabetes by streptozotocin. Motor and sensory nerve conduction velocities were used to gauge nerve dysfunction. Immunocytochemistry, fluorescence in situ hybridisation (FISH) and PCR analysis of dorsal root ganglia (DRG) were employed to monitor outcome. Results We found that loss of TNF-α in BM only protected mice from DPN. We developed a strategy to delete TNF-α specifically in PI-BMDCs, and found that PI-BMDC-specific Conclusions/interpretation BMDC-specific TNF-α is essential for DPN development; its selective removal from a small PI-BMDC subpopulation protects against DPN. The pathogenicity of PI-BMDC-derived TNF-α may have important therapeutic implications.