Transplantation Biology Research Articles

Biosynthesized Gold Nanoparticles: In Vivo Study of Near-Infrared Fluorescence (NIR)-Based Bio-imaging and Cell Labeling Applications.

Near infrared (NIR) fluorescence imaging is a striking imaging modality for biomedical and clinical applications due to its deep tissue penetration and low phototoxicity. The major issue with NIR dyes is their non-specific distribution and requirement of tagging with biomolecules for specific tissue localization. Till now, there have been no imaging agents available that can distribute into a specific organ without the need for targeted ligands, which remains as an unmet clinical need. In the present study, we demonstrate that the Zinnia elegans plant extract (abbreviated as ZE) assisted synthesis of highly biocompatible gold nanoparticles (AuZE), leading to their non-invasive bio-imaging applications in the NIR region (red at 820 nm emission: NIR region). AuZE and ZE both exhibited green fluorescence at 350 nm excitation and red fluorescence in the NIR region (710 nm). We verified the source of this fluorescence, which originates from the fluorescent molecules present in the ZE extract. After intraperitoneal administration in C57BL6 mice, very interestingly, AuZE is distributed into the brain of C57BL6 mice without the need for any targeted ligand and exhibited bright red fluorescence in the NIR region (710 nm excitation, 820 nm emission) as evidenced by non-invasive imaging as well as ICPOES techniques. We further explored the activity of ZE and AuZE as cell labeling agents (B16F10 cells were pre-incubated with AuZE and implanted into mice, and the fluorescence was monitored), which could be applicable for graft transplantation biology. To the best of our knowledge, this is the first report that demonstrates the versatile applications of green synthesized gold nanoparticles using a ZE extract. Considering these exciting results and fruitful outcomes, the ZE and AuZE NPs would stand as an alternative imaging agent to commercially available NIR dyes and change the conventional fluorescence-based bio-imaging strategies. Therefore, the biosynthesized AuNPs open new directions for future research to explore these latest observations in the field of disease diagnosis and therapy.

The Identity Card of T Cells-Clinical Utility of T-cell Receptor Repertoire Analysis in Transplantation.

There is a clear medical need to change the current strategy of "one-size-fits-all" immunosuppression for controlling transplant rejection to precision medicine and targeted immune intervention. As T cells play a key role in both undesired graft rejection and protection, a better understanding of the fate and function of both alloreactive graft-deteriorating T cells and those protecting to infections is required. The T-cell receptor (TCR) is the individual identity card of each T cell clone and can help to follow single specificities. In this context, tracking of lymphocytes with certain specificity in blood and tissue in clinical follow up is of especial importance. After overcoming technical limitations of the past, novel molecular technologies opened new avenues of diagnostics. Using advantages of next generation sequencing, a method was established for T-cell tracing by detection of variable TCR region as identifiers of individual lymphocyte clones. The current review describes principles of laboratory and computational methods of TCR repertoire analysis, and gives an overview on applications for the basic understanding of transplant biology and immune monitoring. The review also delineates methodological pitfalls and challenges. With the outlook on prediction of antigens in immune-mediated processes including those of unknown causative pathogens, monitoring the fate and function of individual T cell clones, and the adoptive transfer of protective effector or regulatory T cells, this review highlights the current and future capability of TCR repertoire analysis.

Immunology's Coming of Age.

This treatise describes the development of immunology as a scientific discipline with a focus on its foundation. Toward the end of the nineteenth century, the study of immunology was founded with the discoveries of phagocytosis by Elias Metchnikoff, as well as by Emil Behring's and Paul Ehrlich's discovery of neutralizing antibodies. These seminal studies were followed by the discoveries of bacteriolysis by complement and of opsonization by antibodies, which provided first evidence for cooperation between acquired and innate immunity. In the years that followed, light was shed on the pathogenic corollary of the immune response, describing different types of hypersensitivity. Subsequently, immunochemistry dominated the field, leading to the revelation of the chemical structure of antibodies in the 1960s. Immunobiology was preceded by transplantation biology, which laid the ground for the genetic basis of acquired immunity. With the identification of antibody producers as B lymphocytes and the discovery of T lymphocytes as regulators of acquired immunity, lymphocytes moved into the center of immunologic research. T cells were shown to be genetically restricted and to regulate different leukocyte populations, including B cells and professional phagocytes. The discovery of dendritic cells as major antigen-presenting cells and their surface expression of pattern recognition receptors revealed the mechanisms by which innate immunity instructs acquired immunity. Genetic analysis provided in-depth insights into the generation of antibody diversity by recombination, which in principle was shown to underlie diversity of the T cell receptor, as well. The invention of monoclonal antibodies not only provided ultimate proof for the unique antigen specificity of the antibody-producing plasma cell, it also paved the way for a new era of immunotherapy. Emil Behring demonstrated cure of infectious disease by serum therapy, illustrating how clinical studies can stimulate basic research. The recent discovery of checkpoint control for cancer therapy illustrates how clinical application benefits from insights into basic mechanisms. Last not least, perspectives on immunology progressed from a dichotomy between cellular-unspecific innate immunity and humoral-specific acquired immunity, toward the concept of complementary binarity.

Microbiological profile of transplant recipients in a tertiary care hospital in South India

Introduction: Infections are the leading cause of morbidity and mortality in transplant recipients. Advances in transplantation biology, organ procurement, surgical techniques, and immunosuppressive therapy have made organ transplantation an effective option for the management of organ failure, with a 1-year survival >60%-80%. However, infection remains one of the most challenging complications of transplantation. Materials & Methods: A total of 1156 clinical specimens from 300 patients who under-went solid organ (renal, liver, heart) & HSCT at Nizams Institute of Medical Sciences over a period of one year were included in the study. The specimens were investigated for microbiological staining, culture, antimicrobial susceptibility testing (AST) and Galactomannan (GM). Samples were processed as per the standard procedures. Results: Of the 1156 specimens received from Solid Organ Transplant/ Haematopoietic Stem Cell Transplant recipients, the majority were fromRenal transplant recipients (n= 1107, 95.76%) followed by HSCT (n=38, 3.28%). The rest were from recipients of liver (n=8), heart (n= 2) and heart- lung (n=1). About 63 showed growth on bacterial or fungal culture. SOT - 60 were culture positive, all were from renal transplant recipients. Most were UTI (n= 32, 53.3%) followed by Blood Stream Infection (n= 13, 21.6%). The other infections seen were pneumonia, wound infection.Of the bacterial isolates (n=49) gram negative- 40 (81.6%) gram positive- 9 (18.4%). E.coli was the predominant isolate (21, 52.5%). Drug resistance was seen in 19 isolates (38.77%), of which 6 were ESBL (31.5%), 13 multi drug resistant (68.4%). Mycobacteria- detected in 9 (n= 52 samples) of which 8 showed M. tuberculosis and one M. abscessus. MDRTB detected in 1 case. 9 patients were diagnosed with Probable Invasive Aspergillosis. Candida parapsilosis reported from a patient with sepsis.GMS stain showed P. carinii in one patient. HSCT-3 bacterial isolates were reported of which one strain was resistant to carbapenems. One Probable case of Invasive Aspergillosis reported. Conclusion: Urinary tract infections were predominant with most isolates multi drug resistance. Infection control measures should be used to decrease the incidence and bacterial resistance of infections.

Myeloid-derived suppressor cells are bound and inhibited by anti-thymocyte globulin.

Myeloid-derived suppressor cells (MDSCs) inhibit T cell responses and are relevant to cancer, autoimmunity and transplant biology. Anti-thymocyte globulin (ATG) is a commonly used T cell depletion agent, yet the effect of ATG on MDSCs has not been investigated. MDSCs were generated in Lewis Lung Carcinoma 1 tumor-bearing mice. MDSC development and function were assessed in vivo and in vitro with and without ATG administration. T cell suppression assays, RT-PCR, flow cytometry and arginase activity assays were used to assess MDSC phenotype and function. MDSCs increased dramatically in tumor-bearing mice and the majority of splenic MDSCs were of the polymorphonuclear subset. MDSCs potently suppressed T cell proliferation. ATG-treated mice developed 50% fewer MDSCs and these MDSCs were significantly less suppressive of T cell proliferation. In vitro, ATG directly bound 99.6% of MDSCs. CCR7, L-selectin and LFA-1 were expressed by both T cells and MDSCs, and binding of LFA-1 was inhibited by ATG pre-treatment. Arg-1 and PD-L1 transcript expression were reduced 30–40% and arginase activity decreased in ATG-pretreated MDSCs. MDSCs were bound and functionally inhibited by ATG. T cells and MDSCs expressed common Ags which were also targets of ATG. ATG may be helpful in tumor models seeking to suppress MDSCs. Alternatively, ATG may inadvertently inhibit important T cell regulatory events in autoimmunity and transplantation.

Genetic Variants in Preeclampsia: Lessons From Studies in Latin-American Populations.

Placental vascularization is a tightly regulated physiological process in which the maternal immune system plays a fundamental role. Vascularization of the maternal-placental interface involves a wide range of mechanisms primarily orchestrated by the fetal extravillous trophoblast and maternal immune cells. In a healthy pregnancy, an immune cross-talk between the mother and fetal cells results in the secretion of immunomodulatory mediators, apoptosis of specific cells, cellular differentiation/proliferation, angiogenesis, and vasculogenesis, altogether favoring a suitable microenvironment for the developing embryo. In the context of vasculopathy underlying common pregnancy disorders, it is believed that inefficient invasion of extravillous trophoblast cells in the endometrium leads to a poor placental blood supply, which, in turn, leads to decreased secretion of angiogenic factors, hypoxia, and inflammation commonly associated with preterm delivery, intrauterine growth restriction, and preeclampsia. In this review, we will focus on studies published by Latin American research groups, providing an extensive review of the role of genetic variants from candidate genes involved in a broad spectrum of biological processes underlying the pathophysiology of preeclampsia. In addition, we will discuss how these studies contribute to fill gaps in the current understanding of preeclampsia. Finally, we discuss some trending topics from important fields associated with pregnancy vascular disorders (e.g., epigenetics, transplantation biology, and non-coding RNAs) and underscore their possible implications in the pathophysiology of preeclampsia. As a result, these efforts are expected to give an overview of the extent of scientific research produced in Latin America and encourage multicentric collaborations by highlighted regional research groups involved in preeclampsia investigation.

Estudio bibliométrico: 45 años de literatura biomédica en trasplante de células madre hematopoyéticas

Introducción: La bibliometría mide variables de la literatura científica que se describen de forma cuantitativa por medio de análisis estadístico; con esta herramienta se busca evidenciar el impacto de los trasplantes de células madre hematopoyéticas en la literatura de los últimos 45 años. Objetivo: Descripción de la literatura médica indexada en MEDLINE desde 1970 hasta 2015 sobre trasplantes de células madre hematopoyéticas. Metodología: Se realizó una búsqueda en la base de datos MEDLINE a través de GoPubMed y Fabumed. La estrategia de búsqueda fue: "Hematopoietic Stem Cell Transplantation"[Majr] AND "1970:2015"[dp]. Las variables analizadas fueron el número de publicaciones por año, revistas, países y porcentaje de publicaciones sobre trasplantes de células madre hematopoyéticas. Resultados: Se recuperaron 23,295 referencias sobre trasplantes de células madre hematopoyéticas. Se identificaron 1,844 revistas diferentes, el mayor número de publicaciones se encontró en Bone Marrow Transplantation con 2,443 publicaciones, seguida de Blood con 1,375 y Biology of Bone Marrow Transplantation con 1,319 referencias. Estados Unidos fue el país con mayor número de publicaciones con 7,491 (32.15%); en Latinoamérica fueron publicados 324 (1.39%). Los descriptores de la literatura más investigados relacionados con el tema fueron: Trasplante de células madre hematopoyéticas con 23,345 publicaciones, humanos con 22,019 y células madre con 17,564. Conclusiones: Las publicaciones sobre trasplantes de células madre hematopoyéticas han incrementado de forma progresiva durante los 45 años estudiados. Los países desarrollados son los que han realizado mayor investigación del tema, en contraste con el número de publicaciones en total. [Rios-Moreno JV, Bueno-Florez SJ, Conde-Hurtado DI, Tarazona N, Sossa-Melo Claudia Lucía. Estudio bibliométrico: 45 años de literatura biomédica en trasplante de células madre hematopoyéticas. MedUNAB 2017-2018; 20(3): 319-326].

Role of IL-18 in transplant biology.

Since pro-inflammatory cytokine IL-18 and its receptor (IL-18R) are closely involved in regulating both adaptive and innate immune responses, it is conceivable that they might play an important role in organ transplantation. IL-18 can stimulate lymphocytes to produce the IFN-γ and regulate macrophage activity, thereby increasing the expression of proinflammatory cytokines including IL-1β, IL-6, CCL4 (macrophage inflammatory protein-1 β), CXCL2 (macrophage inflammatory protein-2), and CCL2 (monocyte chemotactic protein-1). Nevertheless, the IL-18 signaling pathway and its underlying mechanisms remain obscure in transplant biology. This review is to summarize recent advances in our knowledge about the IL-18 signaling pathway and to analyze their functions in transplant-related biology. It was found that IL-18/IL-18R signaling pathway contributed to vascular transplantation, ischemmia/reperfusion, acute kidney injury, and acute rejection of kidney/liver/heart transplantation. IL-18 was a potential CYP3A expression modulator and was capable of affecting tacrolimus pharmacokinetics. Neutralizing IL-18 by its inhibitor IL-18 binding protein could efficiently suppress the production of injury-associated cytokines such as IL-6, TNF-α, IFN-γ, CXCL10 (IFN-γ-inducible protein10), and CX3CL1 (fractalkine) and improve allograft function. Blockade of IL-18 signaling could regulate cardiomyocyte apoptosis and inhibit Th17 cells differentiation. Alteration of IL-18 levels was suggested as a biomarker for predicting ongoing allograft outcome. All these activities could deepen our understanding of immunobiological role of IL-18 and its receptor in the field of organ transplantation. Intervention of IL-18 signaling pathway might be utilized as a therapeutic strategy in clinic.

The Future of Transplant Biology and Surgery

Although allograft organs remain the gold standard for transplantation, the availability of donor organs has forced us to search for alternatives. Regenerative medicine and tissue engineering offer a solution for this issue. Through the use of synthetic scaffolds and organic substrates, we have been able to generate neoorgans for a variety of different body systems. Although these neoorgans remain largely in the experimental phase, the results are promising, and recent technological developments have made production a realistic endeavor on the large scale. In this review, we highlight recent advances in the field of regenerative medicine and their application to the future of transplant surgery. This review contains 6 figures, 2 tables and 42 references Key Words: bioengineering, biomaterial, bioreactor, decellularized organs, organ scaffolds, regenerative medicine, stem cell, three-dimensional printing

Author Index

HLAVolume 91, Issue 5 p. 475-486 AUTHOR INDEX Author Index First published: 18 April 2018 https://doi.org/10.1111/tan.13252Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat Volume91, Issue5Special Issue: Abstracts for the 32nd European Immunogenetics and Histocompatibility Conference and the 25th Annual Meeting of the Italian Society for Immunogenetics and Transplantation Biology (AIBT) Venice Lido, Italy May 9–12, 2018May 2018Pages 475-486 RelatedInformation

Forewords

HLAVolume 91, Issue 5 p. 319-321 FOREWORD Forewords First published: 18 April 2018 https://doi.org/10.1111/tan.13249Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume91, Issue5Special Issue: Abstracts for the 32nd European Immunogenetics and Histocompatibility Conference and the 25th Annual Meeting of the Italian Society for Immunogenetics and Transplantation Biology (AIBT) Venice Lido, Italy May 9–12, 2018May 2018Pages 319-321 RelatedInformation

Abstracts for the 32nd European Immunogenetics and Histocompatibility Conference and the 25th Annual Meeting of the Italian Society for Immunogenetics and Transplantation Biology (AIBT) Venice Lido, Italy May 9-12, 2018.

Abstracts for the 32nd European Immunogenetics and Histocompatibility Conference and the 25th Annual Meeting of the Italian Society for Immunogenetics and Transplantation Biology (AIBT) Venice Lido, Italy May 9-12, 2018.

Impact of Regulatory T Cells on Innate Immune Cells in a Pre-Sensitized Heart Transplant Model

BackgroundAlthough our previous studies revealed the role of Tregs (regulatory T cells) and MDSCs (myeloid-derived suppressor cells) in a pre-sensitized cardiac transplant model, interplay between Tregs and NK cells, neutrophils, and macrophages remain undefined.Material/MethodsMice heart transplantation with skin pre-sensitization was performed, in which prolonged-cold ischemia time (PCI) was used for donor treatment. Syngeneic heterotopic heart transplant recipients with PCI were treated with PC61 (monoclonal anti-CD25 antibodies), adoptive cell transfer with Tregs, and rapamycin.ResultsWe unveiled that both rapamycin treatment and adoptive transfer of Tregs could lead to a remarkable decrease of frequency of splenic Gr1+ cells (P=0.058 and P=0.016, respectively). Although administration of PC61 did not affect frequency of splenic Gr1+ cells, it dramatically increased frequency of splenic F4/80+ macrophages (P=0.052). Intriguingly, use of both exogenous PC61 and rapamycin induced a dramatic augmentation of frequency of Gr-1+ neutrophils in the grafts (PC61: P=0.00029; rapamycin: P=0.0096). Noticeably, all different regimens including PC61, rapamycin, and adoptive transfer of Tregs, consistently resulted in a remarked augmentation of frequency of F4/80+ macrophages within grafts (PC61, P=0.0013; rapamycin, P=0.015; Tregs transfer, P=0.013). Although rapamycin and adoptive transfer of Tregs did not affect frequency of NK1.1+ cells, administration of PC61 dramatically increased frequency of NK1.1+ cells within grafts (P=0.033).ConclusionsTregs depletion or Tregs induced by rapamycin or exogenous cell transfer could affect frequencies of both splenic and intragraft neutrophils, macrophages, and NK cells, but not splenic NK cells. Our data might shed light on understanding sensitized transplant biology.

Tissue-Resident Lymphocytes in Solid Organ Transplantation: Innocent Passengers or the Key to Organ Transplant Survival?

Short-term outcomes of solid organ transplantation have improved dramatically over the past several decades; however, long-term survival has remained static over the same period, and chronic rejection remains a major cause of graft failure. The importance of donor, or "passenger," lymphocytes to the induction of tolerance to allografts was recognized in the 1990s, but their precise contribution to graft acceptance or rejection has not been elucidated. Recently, specialized populations of tissue-resident lymphocytes in nonlymphoid organs have been described. These lymphocytes include tissue-resident memory T cells, regulatory T cells, γδ T cells, invariant natural killer T cells, and innate lymphoid cells. These cells reside in commonly transplanted solid organs, including the liver, kidneys, heart, and lung; however, their contribution to graft acceptance or rejection has not been examined in detail. Similarly, it is unclear whether tissue-resident cells derived from the pool of recipient-derived lymphocytes play a specific role in transplantation biology. This review summarizes the evidence for the roles of tissue-resident lymphocytes in transplant immunology, focussing on their features, functions, and relevance for solid organ transplantation, with specific reference to liver, kidney, heart, and lung transplantation.

Integrative omics for health and disease.

Advances in omics technologies - such as genomics, transcriptomics, proteomics and metabolomics - have begun to enable personalized medicine at an extraordinarily detailed molecular level. Individually, these technologies have contributed medical advances that have begun to enter clinical practice. However, each technology individually cannot capture the entire biological complexity of most human diseases. Integration of multiple technologies has emerged as an approach to provide a more comprehensive view of biology and disease. In this Review, we discuss the potential for combining diverse types of data and the utility of this approach in human health and disease. We provide examples of data integration to understand, diagnose and inform treatment of diseases, including rare and common diseases as well as cancer and transplant biology. Finally, we discuss technical and other challenges to clinical implementation of integrative omics.

Orthotopic Transplantation of Achilles Tendon Allograft in Rats

The biology and function of orthotopic transplantation of Achilles tendon allograft are unknown. Particularly, the revitalization of Achilles allograft is a clinical concern. Achilles allografts were harvested from donor rats and stored at −80 °C. Subcutaneous adipose tissue was harvested from the would-be allograft recipient rats for isolation of mesenchymal stem cells (MSCs). MSCs were cultured with growth differentiation factor-5 (GDF-5) and applied onto Achilles allografts on the day of transplantation. After the native Achilles tendon was resected from the left hind limb of the rats, Achilles allograft, with or without autologous MSCs, was implanted and sutured with calf muscles proximally and calcaneus distally. Animal gait was recorded presurgery and postsurgery weekly. The animals were sacrificed at week 4, and the transplanted Achilles allografts were collected for biomechanical testing and histology. The operated limbs had altered gait. By week 4, the paw print intensity, stance time, and duty cycle (percentage of the stance phase in a step cycle) of the reconstructed limbs were mostly recovered to the baselines recorded before surgery. Maximum load of failure was not different between Achilles allografts, with or without MSCs, and the native tendons. The Achilles allograft supplemented with MSCs had higher cellularity than the Achilles allograft without MSCs. Deposition of fine collagen (type III) fibers was active in Achilles allograft, with or without MSCs, but it was more evenly distributed in the allografts that were incubated with MSCs. In conclusion, orthotopically transplanted Achilles allograft healed with host tissues, regained strength, and largely restored Achilles function in 4 wk in rats. It is therefore a viable option for the reconstruction of a large Achilles tendon defect. Supplementation of MSCs improved repopulation of Achilles allograft, but large animal models, with long-term follow up and cell tracking, may be required to fully appreciate the functional benefits of MSCs.

HLA class I (-A, -B, -C) and class II (-DR, -DQ) polymorphism in the Mauritanian population

BackgroundHLA antigens have been widely studied for their role in transplantation biology, human diseases and population diversity. The aim of this study was to provide the first profile of HLA class I and class II alleles in the Mauritanian population.MethodsHLA typing was carried in 93 healthy Mauritanian blood donors, using single specific primer amplification (PCR-SSP).ResultsOccurrences of the main HLA class I (-A, -B, -C) and class II (-DR, -DQ) antigens in the general population showed that out of the 17 HLA-A allele groups detected, five main HLA-A allele groups: A*02 (18.42%), A*01 (14.04%), A*23 (14.04%), A*30 (13.16%) and A*29 (12.28%) were the most common identified along other 12 relatively minor allele groups. Twenty three allele groups were observed in the locus B of which B*07 (13.46%) was the most prevalent followed by B*15, B*35, B*08 and B*27 all, with a frequency between 7 to 8%. Three prevalent HLA-C allele groups (C*02: 35.09%, C*07: 20.19% and C*06: 13.6%) were detected. The main HLA class II observed allele groups were: DRB1*13 (27.42%), DRB1*03 (24.73%), DRB1*11 (13.98%), DQB1*03 (36.03%), DQB1*02 (22.06%) and DQB1*05 (18.8%). Except for few haplotype in class I (A*02-B*07: 4.45%, A*02-C02: 10%, A*23-C*02: 8.8%, B*07-C*02: 8.8%, B*15-C*02: 8.8%) and in class II (DRB1*13-DQB1*06: 11.94%, DRB1*03-DQB1*02:11.19% and DRB1*03-DQB1*03: 10.45%), the majority of locus combination were in the range of 2–3%. A single predominant haplotype C*02-DRB1*03 (16.67%) was found.ConclusionsThese results, in agreement with previous data using different tissues markers, underlined the ethnic heterogeneity of the Mauritanian population.

Editorial introductions

Current Opinion in Organ Transplantation was launched in 1996. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of organ transplantation is divided into 18 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editors for this issue. SECTION EDITORS Parsia A. VagefiParsia A. VagefiParsia A. Vagefi, MD, is the Associate Surgical Director of Liver Transplantation and the Surgical Director of Living Donor Liver Transplantation at Massachusetts General Hospital. In addition, Dr Vagefi is an Associate Professor of Surgery at Harvard Medical School. Dr Vagefi graduated with a BA in Biology from Johns Hopkins University, followed by medical school at Yale. During medical school, Dr Vagefi was a Howard Hughes Medical Institute Research Fellow at the Transplantation Biology Research Center with Dr David H. Sachs where he investigated large animal models of allotransplantation and xenotransplantation. Dr Vagefi completed his general surgery residency at the Massachusetts General Hospital, followed by an abdominal transplant surgery fellowship at the University of California, San Francisco, where he received the ASTS Novartis Fellowship in Transplantation Award. Dr Vagefi's clinical expertise is in adult and pediatric liver transplantation (including split-liver and living donor liver transplantation) and complex hepatobiliary surgery. Dr Vagefi is a Senior Investigator at the Center for Transplantation Sciences, with a research focus on a pre-clinical model of pig-to-baboon liver xenotransplantation, having now achieved the world's longest survival in pig-to-primate liver xenotransplantation utilizing a novel regimen of co-stimulation blockade combined with coagulation factor infusion. Peter FriendPeter FriendPeter Friend obtained his medical degree (MB BChir) from the University of Cambridge (Magdalene College). He is a Fellow of the Royal College of Surgeons (Eng) and has a doctoral degree (MD) from the University of Cambridge. After specialist training, he spent a year as Assistant Visiting Professor of Surgery, Indiana University, USA, initiating the Indiana liver transplant programme. In 1989, he returned to the UK as Lecturer in Surgery (Honorary Consultant Surgeon), University of Cambridge; he was also Fellow and Director of Studies in Medicine, Magdalene College, Cambridge. In 1999, he was appointed as Professor of Transplantation, University of Oxford (Honorary Consultant Surgeon); he is also Director of the Oxford Transplant Centre and Fellow of Green Templeton College. Peter Friend's clinical commitments include organ transplantation (kidney, pancreas, intestine) and hepatobiliary surgery. He heads a translational research group focusing on organ perfusion (liver/kidney), novel immunosuppressive strategies and pancreas transplantation. He is author of more than 200 scientific papers on clinical transplantation, immunosuppression, monoclonal antibodies, xenotransplantation, and liver perfusion. He is the Royal College of Surgeons national specialist lead for transplantation research. He is a past-President of the British Transplantation Society. Kathy Lee CoffmanKathy Lee CoffmanDr Kathy Coffman is an attending psychiatrist at the Cleveland Clinic Foundation, USA. She attended Wayne State School of Medicine, did an internship in Internal Medicine at Michael Reese Hospital in Chicago, and a psychiatry residency at the University of Chicago. She also did a two-year fellowship in Consultation Liaison Psychiatry at the University of Michigan. She is board certified in addiction psychiatry, geriatric psychiatry and psychosomatic medicine. She has been involved with the field of transplant psychiatry since her residency over the last twenty years. Dr Coffman's research interests include maintaining sobriety in alcoholic liver transplant recipients, HIV, and psychological issues in lung disease. She is a current member of the psychiatry committee for the National Board of Psychiatry and Neurology for development of test questions for the US Medical Licensing Examination. She has been involved in grant review for the National Institutes of Mental Health, and has been a reviewer for Psychomatics and other journals.

Self-Destructive Behavior among Full-Donor Blood and Marrow Grafts and the Association with Long-Term Graft Function

Self-Destructive Behavior among Full-Donor Blood and Marrow Grafts and the Association with Long-Term Graft Function

NKT-cell glycolipid agonist as adjuvant in synthetic vaccine

NKT cells are CD1d-restricted, glycolipid antigen-reactive, immunoregulatory T lymphocytes that can serve as a bridge between the innate and adaptive immunities. NKT cells have a wide range of therapeutic application in autoimmunity, transplant biology, infectious disease, cancer, and vaccinology. Rather than triggering “danger signal” and eliciting an innate immune response, αGalCer-based NKT-cell agonist act via a unique mechanism, recruiting NKT cells which play a T helper-like role even without peptide as Th epitope. Importantly, the non-polymorphism of CD1d render glycolipid a universal helper epitope, offering the potential to simplify the vaccine construct capable of eliciting consistent immune response in different individuals. This review details recent advances in the design of synthetic vaccines using NKT-cell agonist as adjuvant, highlighting the role of organic synthesis and conjugation technique to enhance the immunological actives and to simplify the vaccine constructs.