Xiaofeng Ye

Enhancement of Mesenchymal Stem Cell Attachment to Decellularized Porcine Aortic Valve Scaffold by In Vitro Coating with Antibody Against CD90: A Preliminary Study on Antibody-Modified Tissue-Engineered Heart Valve

The importance of cell adhesion to the scaffold in the tissue-engineered heart valve remains to be determined. The current study examined the feasibility of conjugating antibody against CD90 to a decellularized porcine aortic valve scaffold and binding mesenchymal stem cells to that scaffold through interaction with a cell surface antigen. After decellularization, the porcine aortic valve was reacted with biotin, avidin, and biotinylated anti-rat CD90 antibody sequentially and inserted into a laminar flow system used to test the effect of laminar shear stress. Rat bone mesenchymal stem cells (BMSC) were injected and circulated in a flow system to study the ability of anti-CD90 antibody to trap and immobilize cells on the valve surface. The results demonstrated that anti-CD90 antibody on the valve surface remains bound, even under high shear conditions. Compared with the control valve (no antibody), the modified (antibody-coated) valve immobilized significantly more rat BMSC (p < 0.05). Thus, the avidin-biotin system can be used to attach anti-CD90 antibody to these valves, and the bound antibody can immobilize rat BMSC in a flow chamber, suggesting that antibody-modified scaffolds might be used to fabricate shear stress-resistant, tissue-engineered heart valves.

The effect of Heparin-VEGF multilayer on the biocompatibility of decellularized aortic valve with platelet and endothelial progenitor cells.

The application of polyelectrolyte multilayer films is a new, versatile approach to surface modification of decellularized tissue, which has the potential to greatly enhance the functionality of engineered tissue constructs derived from decellularized organs. In the present study, we test the hypothesis that Heparin- vascular endothelial growth factor (VEGF) multilayer film can not only act as an antithrombotic coating reagent, but also induce proliferation of endothelial progenitor cells (EPCs) on the decellularized aortic heart valve. SEM demonstrated the adhesion and geometric deformation of platelets. The quantitative assay of platelet activation was determined by measuring the production of soluble P-selectin. Binding and subsequent release of heparin and VEGF from valve leaflets were assessed qualitatively by laser confocal scanning microscopy and quantitatively by ELISA methods. Human blood derived EPCs were cultured and the adhesion and growth of EPCs on the surface modified valvular scaffolds were assessed. The results showed that Heparin-VEGF multilayer film improved decellularized valve haemocompatibility with respect to a substantial reduction of platelet adhesion. Release of VEGF from the decellularized heart valve leaflets at physiological conditions was sustained over 5 days. In vitro biological tests demonstrated that EPCs achieved better adhesion, proliferation and migration on the coatings with Heparin-VEGF multilayer film. Combined, these results indicate that Heparin-VEGF multilayer film could be used to cover the decellularized porcine aortic valve to decrease platelet adhesion while exhibiting excellent EPCs biocompatibility.

17β-Estradiol enhances the recruitment of bone marrow-derived endothelial progenitor cells into infarcted myocardium by inducing CXCR4 expression

BACKGROUND 17β-Estradiol (E2) has been thought to produce cardioprotective effects by mediating bone marrow-derived endothelial progenitor cells (EPC) for cardiac repair in the setting of acute myocardial infarction (AMI). However, the underlying mechanism of action of E2 on EPC remains unclear. CXCR4 is a critical modulator in homing of EPC. Accordingly, we hypothesized that E2 exerts beneficial effects through enhancing EPC homing to infarcted myocardium via mediating CXCR4 pathway. METHODS AND RESULTS Migratory capacity and CXCR4 expression of EPC from ovariectomized BALB/C mice were detected after being incubated with various E2 concentrations for various incubation times. For in vivo studies, EPC were labeled with superparamagnetic ion oxide (SPIO) for tracing, and ovariectomized mice were grouped (n=11) after inducing AMI to receive saline without cells or with 3 × 10(6) non-preconditioned EPC, 100 nmol/L E2 preconditioned EPC, CXCR4 inhibitor AMD3100 (5 μg/mL) preconditioned EPC, or EPC pretreated with E2 plus AMD3100. The number of homing EPC in infarcted myocardium and left ventricular (LV) function, dimensions and fibrosis were measured. In vitro data showed that E2 increased migratory activity and functional CXCR4 expression of EPC. However, these effects were completely blocked by AMD3100. In vivo data in E2 group displayed a greater number of homing EPC, decreased fibrosis of LV, and significant improvement in cardiac function. Nevertheless, effects of E2 preconditioning were abrogated by AMD3100. CONCLUSIONS We conclude that E2 enhances the recruitment of EPC into infarcted myocardium by up-regulating functional CXCR4 expression, resulting in improving recovery after myocardial infarction.

Primary malignant pericardial mesothelioma—a rare cause of superior vena cava thrombosis and constrictive pericarditis

Primary malignant pericardial mesothelioma (PMPM) is an extremely rare, highly lethal and often misdiagnosed tumor. We report a 60-year-old woman complaining of dry cough, shortness of breath and exertional dyspnea due to a large pericardial effusion. The pericardial fluid volume declined after pericardiocentesis; analysis of the fluid revealed malignant cells and was negative for tuberculosis. Subsequently, the patient developed a compression of the superior vena cava and pericardial constriction. The patients symptoms marginally improved after partial pericardiectomy, and a diagnosis of pericardial mesothelioma was made on pathology. However, her symptoms continued to aggravate, and she died 8 months after presentation. Pericardial mesothelioma should be discovered earlier to treat patients who develop repeatedly pericardial effusion after pericardiocentesis and pericardial tamponade or those develop constrictive pericarditis.

Robot-assisted coronary artery bypass grafting improves short-term outcomes compared with minimally invasive direct coronary artery bypass grafting

BACKGROUND Robot-assisted coronary artery bypass grafts (RACAB) utilizing the da Vinci surgical system are increasingly used and allow the surgeon to conveniently harvest internal mammary arteries (IMAs). The aim of this study was to compare the outcomes of off-pump RACAB and minimally invasive direct coronary artery bypass grafting (MIDCAB) in the short and medium term. METHODS We performed a retrospective review of 132 patients with single- or multiple-vessel coronary artery disease who underwent minimally invasive off-pump CABG (OPCAB) between May 2009 and May 2014. The patients were divided into two groups based on the surgical approach, MIDCAB and RACAB group. The anastomosis of the left internal mammary artery (LIMA) to the left anterior descending artery (LAD) was performed as regular OPCAB through the incision on the beating heart using regular stabilization devices (Genzyme Corporation). The preoperative, intraoperative, postoperative, and follow-up data, including major adverse cardiac and cerebrovascular events (MACCE), were compared. RESULTS The preoperative data were similar. RACAB significantly shorten the intensive care unit (ICU) stay and postoperative compared with the MIDCAB group (P<0.05). There were 12 (19.7%) patients treated with a two-stage hybrid procedure in the MIDCAB group and 34 (47.9%) patients in the RACAB group (P=0.001). Thirty-day mortality was 1.6% in the MIDCAB group. There were 9 (14.7%) MIDCAB patients and 2 (2.8%) RACAB patients (P=0.013) that developed new arrhythmia. The two groups showed comparable mid-term survival (P=0.246), but the MACCEs were significantly different (P=0.038). CONCLUSIONS RACAB may be a valuable alternative for patients requiring single or simple multi-vessel coronary artery bypass grafting (CABG). Although the mid-term mortality outcomes are similar, RACAB improves short-term outcomes and mid-term MACCE-free survival compared with MIDCAB.

Impact of decellularization on porcine myocardium as scaffold for tissue engineered heart tissue

Decellularized myocardium has been proposed to construct tissue engineered heart tissue, providing the advantage of natural extracellular architecture. Various decellularization protocols have been developed, but the impact of individual decellularization reagent in the protocol remains unclear. The aim of this study is to evaluate the structural impact of three commonly used decellularization reagents on the porcine myocardium. We decellularized porcine heart tissue with trypsin, Triton X-100 or SDS, and analyzed the morphological characteristics of the remaining tissue by SEM, AFM and two-photon LSM. We further recellularized the scaffold with rat myocardial fibroblasts and cardiomyocytes separately. According to the H&E staining and DNA quantification, SDS decellularized more efficiently in comparison to the other two reagents. Moreover, we found distinct surface microarchitecture differences among groups. The changed structure of tissue might result in varied proliferation myocardial fibroblasts and biophysical performance of the engineered heart tissue. This study demonstrated that the microstructure of decellularized porcine heart tissue vary with decellularization agents. Compared to trypsin and Triton X-100, SDS not only decellularized more efficiently but also preserved the biocompatible microstructure of ECM for recellularization.

Spatiotemporal delivery of nanoformulated liraglutide for cardiac regeneration after myocardial infarction

The local, intramyocardial injection of proteins into the infarcted heart is an attractive option to initiate cardiac regeneration after myocardial infarction (MI). Liraglutide, which was developed as a treatment for type 2 diabetes, has been implicated as one of the most promising protein candidates in cardiac regeneration. A significant challenge to the therapeutic use of this protein is its short half-life in vivo. In this study, we evaluated the therapeutic effects and long-term retention of liraglutide loaded in poly(lactic-co-glycolic acid)–poly(ethylene glycol) (PLGA–PEG) nanoparticles (NP-liraglutide) on experimental MI. PLGA–PEG nanoparticles (NPs) have been shown to efficiently load liraglutide and release bioactive liraglutide in a sustained manner. For in vitro test, the released liraglutide retained bioactivity, as measured by its ability to activate liraglutide signaling pathways. Next, we compared the effects of an intramyocardial injection of saline, empty NPs, free liraglutide and NP-liraglutide in a rat model of MI. NPs were detected in the myocardium for up to 4 weeks. More importantly, an intramyocardial injection of NP-liraglutide was sufficient to improve cardiac function (P<0.05), attenuate the infarct size (P<0.05), preserve wall thickness (P<0.05), promote angiogenesis (P<0.05) and prevent cardiomyocyte apoptosis (P<0.05) at 4 weeks after injection without affecting glucose levels. The local, controlled, intramyocardial delivery of NP-liraglutide represents an effective and promising strategy for the treatment of MI.

Tissue-engineered mitral valve chordae tendineae: Biomechanical and biological characterization of decellularized porcine chordae

Chordae tendineae are essential for maintaining mitral valve function. Chordae replacement is one of the valve repair procedures commonly used to treat mitral valve regurgitation. But current chordae alternatives (polytetrafluoroethylene, ePTFE) do not have the elastic and self-regenerative properties. Moreover, the ePTFE sutures sometimes fail due to degeneration, calcification and rupture. Tissue-engineered chordae tendineae may overcome these problems. The utility of xenogeneic chordae for tissue-engineered chordae tendineae has not yet been adequately explored. In this study, polyelectrolyte multilayers (PEM) film modified decellularized porcine mitral valve chordae (PEM-DPC) were developed to explore tissue-engineered chordae tendineae as neochordae substitutes. Fresh porcine mitral chordae were decellularized and reserved the major elastic fiber and collagen components. Decellularized chordae with a PEM film were produced with chitosan-heparin by a lay-by-lay technique. Mesenchymal stem cells and vascular endothelial cells could grow well on the surface of the PEM-DPC. The superior biomechanical properties of PEM-DPC were proved with good flexibility and strength both in vitro and in vivo. PEM-DPC can be developed for potential alternative mitral valve chordae graft.

Off-pump coronary artery bypass surgery outcomes in patients with ischaemic left ventricular systolic dysfunction with or without detected viable myocardium

OBJECTIVES The prognostic value of myocardial viability before coronary bypass grafting remains controversial. The present study evaluated the effects of off-pump coronary artery bypass (OPCAB) grafting on patients with coronary artery disease (CAD) with or without viable myocardium (VM) preoperatively detected via nuclear imaging. METHODS A total of 115 consecutive patients with 3-vessel disease and impaired left ventricular ejection fraction (LVEF ≤ 45%) who underwent OPCAB grafting were recruited in this prospective study. The patients were divided into 2 groups based on myocardial viability, the non-viable myocardium (NVM, 55 patients) and VM (60 patients) groups. Positron emission tomography and radionuclide imaging examination were applied to evaluate the myocardium viability. A Kaplan-Meier analysis was conducted to evaluate the 1-year survival rate. RESULTS The preoperative data were similar between groups. An improvement in the LVEF was observed in both groups 12 months after OPCAB grafting (P < 0.05). A binary logistic regression revealed that NVM was an independent predictor of a 5% improvement in LVEF at 6 months (P = 0.012). The rate of main adverse cardiovascular and cerebrovascular events (MACCEs) rate at 1 year was similar between the 2 groups (P = 0.06). At 1 year, the death rates were 14.5% in the NVM group and 5% in the VM group (P = 0.17). A Cox regression analysis revealed that NVM and age were independent predictors of mortality [the hazard ratio for death associated with NVM and age were 1.62, 95% confidence interval (CI) = 1.16-2.89, P = 0.036 and 1.05, 95% CI = 0.98-1.12, P =0.025, respectively]. CONCLUSIONS The MACCEs and mortality rates of the NVM group were higher than those of the VM group. However, OPCAB surgery improved LVEF, regardless of myocardium status. Therefore, the assessment of myocardial viability might not be the sole deciding factor in decision-making process regarding OPCAB surgery.

Plasma levels of growth differentiation factor-15 are associated with myocardial injury in patients undergoing off-pump coronary artery bypass grafting.

Growth differentiation factor-15 (GDF-15) has recently emerged as a risk predictor in patients with cardiovascular diseases. We therefore aimed to investigate the role of GDF-15 in the occurrence of cardiac injury during off-pump coronary artery bypass grafting (OPCAB). 55 consecutive patients with coronary artery diseases were recruited in this prospective, observational study. All patients were operated for OPCAB surgery. Serial blood samples were collected preoperatively, 12 hours and 36 hours after surgery. GDF-15, together with C-reactive protein, cardiac troponin I, creatine kinase MB and N-terminal pro B-type natriuretic peptide levels in plasma were measured at each time-point. GDF-15 levels increased significantly at 12 hours after surgery, attaining nearly 2.5 times the baseline levels (p < 0.001). Postoperative GDF-15 levels correlated positively with cTnI (p = 0.003) and EuroSCORE II (p = 0.013). According to the ROC curves, postoperative plasma GDF-15 was found to be the best biomarker to predict perioperative cardiac injury, compared with cTnI, CK-MB and EuroSCORE II. Circulating GDF-15 is a promising novel biomarker for identifying perioperative myocardial injury in patients undergoing OPCAB.