Robotically-assisted Coronary Artery Surgery with and Without Cardiopulmonary Bypass - from First Clinical Use to Endoscopic Operation

Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. Jul, 2002  |  Pubmed ID: 12118209

Recently, the ZEUS(tm) Robotic Surgical System has been introduced to increase the precision of endoscopic cardiac surgery. This study investigated its clinical use for endoscopic coronary artery bypass grafting.

Comparison of Two Stabilizer Concepts for Off-pump Coronary Artery Bypass Grafting

The Annals of Thoracic Surgery. Aug, 2002  |  Pubmed ID: 12173835

This study was designed to evaluate the efficacy of two different stabilizer concepts for off-pump coronary artery bypass grafting.

Early and Midterm Results After Coronary Artery Bypass Grafting with and Without Cardiopulmonary Bypass: Which Patient Population Benefits the Most?

The Heart Surgery Forum. 2003  |  Pubmed ID: 12716586

We present our early and midterm results with off-pump coronary artery bypass grafting (OPCAB) on the beating heart and with conventional coronary artery bypass grafting (CABG) and compare patient outcomes for both procedures.

New Technique for Chest Opening in Mice: U-sternotomy

Microsurgery. 2003  |  Pubmed ID: 12833331

In cardiac xenotransplantation, transfections with recombinant adeno-associated viruses could be a promising way of modulating the cardiomyocyte genome. Proteins like TRAIL, hDAF, Il-10, Il-4, and beta-galactosidase may be expressed on cardiomyocyte surfaces in order to prevent cellular rejection processes. However, after intracoronary perfusion with transfecting viruses, it takes up to 4 weeks before expression of the transgene can be detected. Mouse models have been established to create reliable transfection protocols. Currently, the major problem involves performing the intraaortic injection in mice without causing a lethal pneumothorax. Here we describe a new technique for chest opening to safely reach the mouse ascending aorta without opening the pleural space. This U-sternotomy reduces the risk of animal death and therefore the amount of quite expensive virus solutions needed.

Successful Resection of a Symptomatic Right Ventricular Lipoma

The Annals of Thoracic Surgery. Oct, 2003  |  Pubmed ID: 14530040

We report the case of a 31-year-old woman with a 4-year history of recurrent palpitations, presenting with an increased frequency of paroxysms caused by ventricular tachycardias during pregnancy. A cardiac tumor of unknown origin infiltrating the right ventricle was diagnosed. Three weeks after prophylactic abrasion the tumor was totally excised with the use of cardiopulmonary bypass including restoration of the right ventricular wall and the tricuspid valve. Histology confirmed diagnosis of a benign cardiac lipoma. The postoperative course was uneventful and the patient was discharged 7 days after surgery. There was no episode of ventricular tachycardias during the 6-month follow-up.

Immunosuppression with FK778 and Mycophenolate Mofetil in a Rat Cardiac Transplantation Model

Transplantation. Dec, 2003  |  Pubmed ID: 14702537

FK778 blocks the dihydro-orotate dehydrogenase, necessary for pyrimidine synthesis, and mycophenolate mofetil (MMF) inhibits the inosine monophosphate dehydrogenase, a crucial enzyme for purine biosynthesis. Beneficial immunosuppressive effects have been suggested for the combination of both drugs. The Brown Norway-Lewis rat heterotopic heart transplantation model was used. FK778 (5 and 20 mg/kg/day), MMF (10 and 40 mg/kg/day), or a combination of both drugs for 10 days was used for prevention of acute graft rejection. Grafts of untreated animals were rejected after 6.2 +/- 0.4 days. Low-dose FK778 and low-dose MMF administration did not result in a significantly prolonged graft survival (6.7 +/- 0.8 and 8.7 +/- 1.4 days; P=not significant). Grafts of rats treated with high-dose FK778 or high-dose MMF survived significantly longer (17.0 +/- 2.8 and 20.7 +/- 3.8 days; P<0.01). Concomitant use of low-dose FK778 with low-dose MMF produced synergistic interactions (mean survival time 12.3 +/- 2.9 days; P<0.01; combination index=0.85). High-dose drug combination (mean survival time 24.0 +/- 1.4 days) showed antagonistic drug interaction (combination index=1.55) with increased toxic side effects.

The Interaction Between FK778 and Tacrolimus in the Prevention of Rat Cardiac Allograft Rejection is Dose Dependent

Transplantation. Feb, 2004  |  Pubmed ID: 15084926

The synthetic malononitrilamide FK778 inhibits T- and B-cell responsiveness, phagocyte effector function, exerts inhibitory activity against cytomegalovirus, and is thus one of the most promising new immunosuppressive drugs. The aim of this study was to evaluate the combination of FK778 and tacrolimus in a high-responder rat cardiac transplantation model.

FK778 Attenuates Lymphocyte-endothelium Interaction After Cardiac Transplantation: in Vivo and in Vitro Studies

Transplantation. Jul, 2004  |  Pubmed ID: 15257041

The malononitrilamide FK778 is a novel derivate of leflunomide and interacts with T- and B-cell function by inhibiting de novo pyrimidine synthesis. We investigated the effects of FK778 upon acute cardiac allograft rejection and upon adhesion molecule upregulation in experimental transplantation and by using in vitro cell culture.

Video and Robotic-assisted Minimally Invasive Mitral Valve Surgery: a Comparison of the Port-Access and Transthoracic Clamp Techniques

The Annals of Thoracic Surgery. Feb, 2005  |  Pubmed ID: 15680820

In order to assess different surgical techniques for video-assisted minimally invasive mitral valve surgery, a retrospective study was undertaken comparing the Port-Access system (Cardiovations, Ethicon Inc, Somerville, NJ) and the transthoracic clamp technique.

FK778, a Novel Immunosuppressive Agent, Reduces Early Adhesion Molecule Up-regulation and Prolongs Cardiac Allograft Survival

Transplant International : Official Journal of the European Society for Organ Transplantation. Feb, 2005  |  Pubmed ID: 15691275

The adhesion molecules, P-selectin, ICAM-1, and VCAM-1 are important mediators of T-cell adhesion and T-cell co-stimulation. We investigated the effect of the malononitrilamide FK778 on cardiac allograft survival, acute allograft rejection, and adhesion molecule up-regulation in a heterotopic, cardiac transplantation model. Rats received low- or high-dose FK778 or no treatment. Grafts were harvested on the fifth postoperative day for histologic examinations. To assess allograft survival, recipients were treated for a maximum of 10 days and grafts were harvested after cessation of the contractile activity. FK778 low dose showed a mild but significant decrease in mononuclear infiltration but failed to markedly reduce histologic rejection, adhesion molecule up-regulation, or to prolong allograft survival. However, high-dose FK778 treatment significantly reduced early up-regulation of P-selectin, ICAM-1, and VCAM-1, abolished infiltration, reduced histologic rejection and resulted in prolonged cardiac allograft survival. Therefore, FK778 is a novel, highly desirable immunosuppressive drug for transplantation medicine.

The Phytoestrogen BiochaninA Weakens Acute Cardiac Allograft Rejection Without Affecting the Reproductive System

Transplant Immunology. Oct, 2005  |  Pubmed ID: 16223672

Since the two estrogen receptor isoforms ERalpha and ERbeta have been discovered it is unclear by which receptor immunomodulating or feminizing effects are mediated. In this study, the effects of the two selective ERalpha- and ERbeta-agonists ethinylestradiol and biochaninA, respectively, on acute cardiac allograft rejection, uterus growth, vascular adhesion molecule and MHC-II expression were investigated and verified using in vitro cell culture.

FK778 and Tacrolimus Prevent the Development of Obliterative Airway Disease After Heterotopic Rat Tracheal Transplantation

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. Nov, 2005  |  Pubmed ID: 16297791

The effectiveness of the novel immunosuppressive agent FK778 and of tacrolimus to prevent the development of obliterative airway disease (OAD) was investigated in an animal model.

Sirolimus and FK778: a Comparison of Two Anti-proliferative Immunosuppressants for Prevention of Experimental Obliterative Airway Disease

Transplant International : Official Journal of the European Society for Organ Transplantation. Apr, 2006  |  Pubmed ID: 16573547

This study examined the efficacies of sirolimus and the novel immunosuppressive agent FK778 to prevent obliterative airway disease (OAD). Tracheae from Brown-Norway donors were heterotopically transplanted in the greater omentum of Lewis rats. Recipients were treated for 28 days with sirolimus (0.5 or 2 mg/kg), FK778 (5 or 20 mg/kg), or combination regimens (0.5 + 5 mg/kg, 2 + 20 mg/kg). Tracheal segments were evaluated for degree of luminal obliteration, percentage of luminal epithelial cell coverage, and peritracheal infiltration. In vitro smooth muscle cell (SMC) proliferation and migration assays were performed to assess direct nonimmune-related effects of the drugs. Sirolimus 2 mg/kg and FK778 20 mg/kg effectively reduced graft infiltration and prevented airway obliteration, whereas FK778 5 mg/kg was insufficient. Sirolimus 0.5 mg/kg at least showed moderate inhibitory effects on luminal obliteration and graft infiltration. Combination regimens revealed no significant beneficial effects. Both sirolimus and FK778 barely showed preserved epithelial coverage. Within the range of relevant concentrations, FK778 showed more potent anti-proliferative and anti-migratory effects on SMC in vitro than sirolimus. Both agents proved effective to prevent OAD development without preserving relevant amounts of epithelium. The anti-proliferative potency on SMCs seems to be an especially important mechanism for FK778. De novo combination regimens revealed no beneficial interaction and thus remain doubtful.

Heparins Increase Endothelial Nitric Oxide Bioavailability by Liberating Vessel-immobilized Myeloperoxidase

Circulation. Apr, 2006  |  Pubmed ID: 16606792

Neutrophils and monocytes are centrally linked to vascular inflammatory disease, and leukocyte-derived myeloperoxidase (MPO) has emerged as an important mechanistic participant in impaired vasomotor function. MPO binds to and transcytoses endothelial cells in a glycosaminoglycan-dependent manner, and MPO binding to the vessel wall is a prerequisite for MPO-dependent oxidation of endothelium-derived nitric oxide (NO) and impairment of endothelial function in animal models. In the present study, we investigated whether heparin mobilizes MPO from vascular compartments in humans and defined whether this translates into increased vascular NO bioavailability and function.

The Selective Estrogen Receptor-beta Agonist Biochanin A Shows Vasculoprotective Effects Without Uterotrophic Activity

Menopause (New York, N.Y.). May-Jun, 2006  |  Pubmed ID: 16735947

Current hormone therapy in postmenopausal women is associated with uterotrophic activity and cancer-promoting effects. In this experimental study, we compared the effects of the selective estrogen-receptor (ER) beta agonist biochanin A, and the selective ERalpha agonist ethinylestradiol, on the development of intimal hyperplasia after balloon injury and on uterus morphology.

Inhibition of Restenosis Development After Mechanical Injury: a New Field of Application for Malononitrilamides?

Cardiology. 2007  |  Pubmed ID: 17028423

To investigate the efficacy of the malononitrilamide FK778 to prevent vascular smooth muscle cell (SMC) migration/proliferation, and vascular fibrosis, the key events in restenosis development using in vivo and in vitro studies.

FK778 in Experimental Xenotransplantation: a Detailed Analysis of Drug Efficacy

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. Jan, 2007  |  Pubmed ID: 17234520

This study examines the efficacy of FK778 regimens for prevention of different phases of xenograft rejection.

Experimental Orthotopic Tracheal Transplantation: The Stanford Technique

Microsurgery. 2007  |  Pubmed ID: 17326196

The rat heterotopic tracheal transplantation model is widely used as an experimental model to study the development of obliterative airway disease (OAD) and to assess immunosuppressive strategies for chronic rejection. Despite its widespread application, the heterotopic transplantation model does have a number of limitations like the lack of air flow and mucociliary clearance. The present article provides a detailed description of the surgical technique for orthotopic tracheal transplantations, which may share more similarities with lung transplants in humans. The technique is easy to learn, the procedure is well tolerated by the animals, and the grafts develop OAD lesions similar to those of human obliterative bronchiolitis.

Simplified Protocol to Isolate, Purify, and Culture Expand Mesenchymal Stem Cells

Stem Cells and Development. Feb, 2007  |  Pubmed ID: 17348808

Mesenchymal stem cells (MSCs) are widely used for experimental regenerative strategies. Due to their differentiation capacity into mesenchymal lineages, they are a potential cellular source for tissue regeneration. Because there is no specific antigen that can be used to define MSCs directly, there is no consensus about how to isolate them. Here we describe a simple protocol to isolate, purify, and culture expand murine bone marrow MSCs using magnetic cell sorting and plastic adherence. We further show that cytokine supplementation enhances MSC proliferation without jeopardizing their pluripotency.

Techniques for Experimental Heterotopic and Orthotopic Tracheal Transplantations - When to Use Which Model?

Transplant Immunology. Jun, 2007  |  Pubmed ID: 17493528

Different animal models have been developed to study the pathogenesis and treatment of obliterative airway disease (OAD). Here we describe the techniques of heterotopic and orthotopic tracheal transplantations in the rat, comparing the kinetics of systemic host immune response and of histopathologic OAD development.

Fluoroscopy to Assess Late Heart and Lung Perforation by a Permanent Ventricular Pacemaker Lead. A Case Complicated by Isolated Hemothorax

International Journal of Cardiology. Aug, 2008  |  Pubmed ID: 17706810

We report a female patient with a ventricular lead perforation late after implantation. The lead perforated heart and lung parenchyma and caused hemothorax but no cardiac effusion or tamponade. No definitive evidence for lead perforation was found by standard diagnostic assessment. Definitive diagnosis was established by cath-lab fluoroscopy. The surgical treatment including thoracotomy, lead removal, repair suture of the right ventricle and finally placement of an epicardial electrode was successful.

Novel Immunosuppression: R348, a JAK3- and Syk-inhibitor Attenuates Acute Cardiac Allograft Rejection

Transplantation. Mar, 2008  |  Pubmed ID: 18360272

Janus kinase (JAK)3 is crucial for signal transduction downstream of various cytokine receptors in immune cells. This is the first report on the novel JAK3 inhibitor R348.

Introducing the First Polymer-free Leflunomide Eluting Stent

Atherosclerosis. Sep, 2008  |  Pubmed ID: 18295768

We here describe the pharmacological characteristic, in vivo efficacy, and in vitro mechanisms of a polymer-free leflunomide eluting stent in comparison to its rapamycin-coated equivalent.

Prevention and Inhibition but Not Reversion of Chronic Allograft Vasculopathy by FK778

Transplantation. Mar, 2008  |  Pubmed ID: 18360270

This study aimed at investigating the efficacy of the novel immunosuppressant FK778 to prevent the development and progression of chronic allograft vasculopathy (CAV).

A Novel JAK3 Inhibitor, R348, Attenuates Chronic Airway Allograft Rejection

Transplantation. Mar, 2009  |  Pubmed ID: 19295308

This study aimed at investigating the role of a novel JAK3 inhibitor, R348, in the prevention of chronic airway allograft rejection.

Right Ventricular Dysfunction Predicts Poor Outcome Following Hemodynamically Compromising Rejection

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. Apr, 2009  |  Pubmed ID: 19332256

Hemodynamically compromising rejection (HCR) is a major cause of mortality and morbidity after heart transplantation. Right ventricular (RV) function is a strong predictor of outcome in patients with heart failure and myocarditis. The objective of the current study is to determine whether RV dysfunction predicts event-free survival in patients with HCR.

Heart-lung Transplantation in Situs Inversus Totalis

The Annals of Thoracic Surgery. Sep, 2009  |  Pubmed ID: 19699943

Situs inversus totalis is a condition with left-to-right reversal of the viscera combined with dextrocardia. It has long been regarded a contraindication for thoracic transplantation. Reconstruction of the mirror-image systemic venous pathways to accommodate normal donor organs remains the main surgical challenge. Here we present our simplified surgical technique for combined heart-lung transplantation and provide a concise review of the literature.

Hepatocyte Growth Factor or Vascular Endothelial Growth Factor Gene Transfer Maximizes Mesenchymal Stem Cell-based Myocardial Salvage After Acute Myocardial Infarction

Circulation. Sep, 2009  |  Pubmed ID: 19752375

Mesenchymal stem cell (MSC)-based regenerative strategies were investigated to treat acute myocardial infarction and improve left ventricular function.

Alternative Technique for Salvage of Donor Lungs with Insufficient Atrial Cuffs

The Annals of Thoracic Surgery. Oct, 2009  |  Pubmed ID: 19766854

Inadequate left atrial cuff surrounding donor pulmonary veins may present a technical challenge for successful lung transplantation. A simple technique for construction of venous anastomoses during lung transplantation when donor atrial cuff is lacking involves circumferential incorporation of surrounding donor pericardium into the anastomosis without directly suturing or augmenting donor venous structures.

Changing Trends in Infectious Disease in Heart Transplantation

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. Mar, 2010  |  Pubmed ID: 19853478

During the past 25 years, advances in immunosuppression and the use of selective anti-microbial prophylaxis have progressively reduced the risk of infection after heart transplantation. This study presents a historical perspective of the changing trends of infectious disease after heart transplantation.

Mechanisms Behind Local Immunosuppression Using Inhaled Tacrolimus in Preclinical Models of Lung Transplantation

American Journal of Respiratory Cell and Molecular Biology. Oct, 2010  |  Pubmed ID: 19880819

Inhaled immunosuppression with tacrolimus (TAC) is a novel strategy after lung transplantation. Here we investigate the feasibility of tacrolimus delivery via aerosol, assess its immunosuppressive efficacy, reveal possible mechanisms of action, and evaluate its airway toxicity. Rats received 4 mg/kg TAC via oral or inhaled (AER) administration. Pharmacokinetic properties were compared, and in vivo airway toxicity was assessed. Full-thickness human airway epithelium (AE) was grown in vitro at an air-liquid interface. Equal TAC doses (10-1,000 ng) were either added to the bottom chamber (MED) or aerosolized for gas-phase exposure (AER). Airway epithelium TAC absorption, cell toxicity, and interactions of TAC with NFκB activation were studied. Single-photon emission computed tomography demonstrated a linear tracer accumulation within the lungs during TAC inhalation. The AER TAC generated higher lung-tissue concentrations, but blood concentrations that were 11 times lower. Airway histology and gene expression did not reveal drug toxicity after 3 weeks of treatment. In vitro AE exposed to TAC at 10-1,000 ng, orally or AER, maintained its pseudostratified morphology, did not show cell toxicity, and maintained its epithelial integrity, with tight junction formation. The TAC AER-treated AE absorbed the drug from the apical surface and generated lower-chamber TAC concentrations sufficient to suppress activated lymphocytes. Tacrolimus AER was superior to TAC MED at preventing AE IFN-γ, IL-10, IL-13, monocyte chemoattractant protein-1 chemokine (C-C motif) ligand 5 (RANTES) and TNF-α up-regulation. Tacrolimus inhibited airway epithelial cell NFκB activation. In conclusion, TAC can be delivered easily and effectively into the lungs without causing airway toxicity, decreases inflammatory AE cytokine production, and inhibits NFκB activation.

Heart Transplantation in Situs Inversus Totalis

The Journal of Thoracic and Cardiovascular Surgery. Feb, 2010  |  Pubmed ID: 19660287

Asymptomatic Infection with Novel Influenza A/H1N1 Virus in a Heart Transplant Recipient

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. May, 2010  |  Pubmed ID: 20060323

The spectrum of manifestations and management of the novel influenza A/H1N1 virus in transplanted patients is currently of major concern. Asymptomatic infections are less common yet important for spreading of the virus and thus affect containment measures. To our knowledge, there are no reports of asymptomatic infections with influenza A/H1N1 in immunosuppressed patients. We present the first case of a young heart transplant recipient who remained asymptomatic despite positive polymerase chain reaction (PCR) after exposure to individuals with influenza A/H1N1.

Non-volume-loaded Heart Provides a More Relevant Heterotopic Transplantation Model

Transplant Immunology. May, 2010  |  Pubmed ID: 20403439

We aimed to compare two techniques of heterotopic heart transplantation in rats. Non-volume-loaded (NL) and volume-loaded (VL) models were tested for their physiologic and immunologic properties to assess their suitability for transplant studies.

Review of Heart-lung Transplantation at Stanford

The Annals of Thoracic Surgery. Jul, 2010  |  Pubmed ID: 20609821

Long-term survival after heart-lung transplantation was first achieved in 1981 at Stanford and a total of 217 heart-lung transplantations had been performed by June 2008. This review summarizes Stanford's cumulative experience with heart-lung transplantation, demonstrates the progress that has been made, and discusses past and persistent problems. Diagnostic tools and treatment options for infectious diseases and rejection have changed and patient survival markedly improved over the almost three decades. Eight patients lived longer than 20 years. Further options to treat infections and strategies to control bronchiolitis obliterans syndrome, the main causes of early and long-term mortality, respectively, are required to achieve routine long-term survival.

Sustained Inhibition of Epsilon Protein Kinase C Inhibits Vascular Restenosis After Balloon Injury and Stenting

Circulation. Sep, 2010  |  Pubmed ID: 20837910

ε protein kinase C (εPKC) is involved in vascular smooth muscle cell (VSMC) activation, but little is known about its function in vascular pathology. We aimed at assessing the role of εPKC in the development of restenosis.

Immunogenicity and Immunomodulatory Properties of Umbilical Cord Lining Mesenchymal Stem Cells

Cell Transplantation. 2011  |  Pubmed ID: 21054940

We here present an immunologic head-to-head comparison between human umbilical cord lining mesenchymal stem cells (clMSCs) and adult bone marrow MSCs (bmMSCs) from patients >65 years of age. clMSCs had significantly lower HLA class I expression, higher production of tolerogenic TGF-β and IL-10, and showed significantly faster proliferation. In vitro activation of allogeneic lymphocytes and xenogeneic in vivo immune activation was significantly stronger with bmMSCs, whereas immune recognition of clMSCs was significantly weaker. Thus, bmMSCs were more quickly rejected in immunocompetent mice. IFN-γ at 25 ng/ml increased both immunogenicity by upregulation of HLA class I/ HLA-DR expression and tolerogenicity by increasing intracellular HLA-G and surface HLA-E expression, augmenting TGF-β and IL-10 release, and inducing indoleamine 2,3-dioxygenase (IDO) expression. Higher concentrations of IFN-γ (>50 ng/ml) further enhanced the immunosuppressive phenotype of clMSCs, more strongly downregulating HLA-DR expression and further increasing IDO production (at 500 ng/ml). The net functional immunosuppressive efficacy of MSCs was tested in mixed lymphocyte cultures. Although both clMSCs and bmMSCs significantly reduced in vitro immune activation, clMSCs were significantly more effective than bmMSCs. The veto function of both MSC lines was enhanced in escalating IFN-γ environments. In conclusion, clMSCs show a more beneficial immunogeneic profile and stronger overall immunosuppressive potential than aged bmMSCs.

Antibody Response After a Single Dose of an AS03-adjuvanted Split-virion Influenza A (H1N1) Vaccine in Heart Transplant Recipients

Transplantation. May, 2011  |  Pubmed ID: 21358365

Influenza A (H1N1) has emerged as a considerable threat for recipients of organ transplants. Vaccination against the novel influenza A (H1N1) virus has generally been advocated. There is limited experience with AS03-adjuvanted A/H1N1 pandemic influenza vaccines in immunosuppressed patients.

Surgical Technique of Lower Lobe Lung Transplantation

The Annals of Thoracic Surgery. Aug, 2011  |  Pubmed ID: 21801900

Among patients with end-stage lung disease awaiting lung transplantation, pediatric and small adult patients have a significantly lower chance of getting size-matched pulmonary grafts in time because of the severe scarcity of small donors. It is our strategy to perform lobar lung transplantations in small recipients with restrictive pulmonary disease once their clinical status demands urgent transplantation. Here we describe our surgical technique and discuss the benefits and risks of this procedure.

Immunobiology of Naïve and Genetically Modified HLA-class-I-knockdown Human Embryonic Stem Cells

Journal of Cell Science. Sep, 2011  |  Pubmed ID: 21878509

Human embryonic stem cells (hESCs) can serve as a universal cell source for emerging cell or tissue replacement strategies, but immune rejection of hESC derivatives remains an unsolved problem. Here, we sought to describe the mechanisms of rejection for naïve hESCs and upon HLA class I (HLA I) knockdown (hESC(KD)). hESCs were HLA I-positive but negative for HLA II and co-stimulatory molecules. Transplantation of naïve hESC into immunocompetent Balb/c mice induced substantial T helper cell 1 and 2 (Th1 and Th2) responses with rapid cell death, but hESCs survived in immunodeficient SCID-beige recipients. Histology revealed mainly macrophages and T cells, but only scattered natural killer (NK) cells. A surge of hESC-specific antibodies against hESC class I, but not class II antigens, was observed. Using HLA I RNA interference and intrabody technology, HLA I surface expression of hESC(KD) was 88%-99% reduced. T cell activation after hESC(KD) transplantation into Balb/c was significantly diminished, antibody production was substantially alleviated, the levels of graft-infiltrating immune cells were reduced and the survival of hESC(KD) was prolonged. Because of their very low expression of stimulatory NK ligands, NK-susceptibility of naïve hESCs and hESC(KD) was negligible. Thus, HLA I recognition by T cells seems to be the primary mechanism of hESC recognition, and T cells, macrophages and hESC-specific antibodies participate in hESC killing.

Human Leukocyte Antigen I Knockdown Human Embryonic Stem Cells Induce Host Ignorance and Achieve Prolonged Xenogeneic Survival

Circulation. Sep, 2011  |  Pubmed ID: 21911816

Although human embryonic stem cells (hESC) have enormous potential for cell replacement therapy of heart failure, immune rejection of hESC derivatives inevitably would occur after transplantation. We therefore aimed to generate a hypoantigeneic hESC line with improved survival characteristics.

Cardiac Paraganglioma: Diagnostic and Surgical Challenges

Journal of Cardiac Surgery. Jan, 2012  |  Pubmed ID: 22273468

Abstract  Primary cardiac paragangliomas are rare extra-adrenal tumors. Though they account for less than 1% of all primary cardiac tumors, they are considerable sources of morbidity and mortality. In this case review, we discuss the challenges associated with the diagnosis and management of cardiac paragangliomas. (J Card Surg 2012;**:1-5).