Transplantation Biology Research Articles

From Kidney Transplants to Vascularized Composite Allografts: The Role of the Plastic Surgeon in Transplantation

In 1954, plastic surgeon Dr Joseph Murray performed the first successful organ transplant between identical twins. Today solid organ transplants are performed routinely and offer a curative option for patients with end stage organ failure. For his pioneering work in transplantation biology, Dr Murray remains the only plastic surgeon to have been awarded the Nobel Prize in Medicine.The success of modern day transplants has allowed transplantation to be applied more broadly. In particular, vascularized composite allografts (VCAs), including face and hand transplants, have emerged over the past 15 y. These have been used for reconstruction of patients with extensive disfigurements. Despite these great successes, the use of chronic immunosuppression by transplant recipients is accompanied by the risk of malignancy, organ toxicity and infection. Current research efforts by transplant physicians and plastic surgeons are aimed at reducing and subsequently eliminating the burden of life-long immunosuppression.Thi...

Role of IL-21 signaling pathway in transplant-related biology.

Since pro-inflammatory cytokine IL-21 and its receptor (IL-21R) are closely involved in regulating both innate and adaptive immune responses, it is conceivable that they may play important roles in the field of organ transplantation. IL-21/IL21-R regulates immune activities of CD8+ T cells, Tfh cells, Th17 cells, B cells, NK cells, dendritic cells and stimulates dendritic cells to produce high level of IL-6, TNF-alpha, and CCL2. However, their roles and underlying mechanisms remain obscure. Our present study is the first describing the role of IL-21 signaling pathway in transplant biology. It was found that IL-21/IL-21R signaling pathways contribute to the processes of ischemia/reperfusion and acute rejection of liver or kidney transplantation. IL-21 is capable of regulating B cell function and immunoglobulin production, driving CD8+ T cell expansion, regulating Th17 and dendritic cell function. Deficiency of IL-21 may cause autoimmunity and infectious disease in clinical-scenario patients. It is known that CD8+ T cells, Th17, and dendritic cells are closely involved in cardiac transplant tolerance. Our own original experimental research on mouse cardiac transplantation manifested that allograft survival could be significantly prolonged in the IL-21R deficient recipients. All these can deepen our understanding of immunobiological role of IL-21 and its receptor in the field of transplantation. Intervention of IL-21 signaling pathway may apparently regulate immunoresponses in vivo, which can be subsequently utilized as a therapeutic strategy in clinic.

Could a dye offer a cheap and simple approach to detect bladder cancer using white-light cystoscopy?

BJU InternationalVolume 116, Issue 3 p. 466-467 Science Made Simple Could a dye offer a cheap and simple approach to detect bladder cancer using white-light cystoscopy? Linda M. McLatchie, Corresponding Author Linda M. McLatchie Transplantation, Immunology and Mucosal Biology, King's College, London, UK Correspondence: Linda M. McLatchie, Transplantation, Immunology and Mucosal Biology, King's College London, London SE1 9RT, UK. e-mail: [email protected]Search for more papers by this author Linda M. McLatchie, Corresponding Author Linda M. McLatchie Transplantation, Immunology and Mucosal Biology, King's College, London, UK Correspondence: Linda M. McLatchie, Transplantation, Immunology and Mucosal Biology, King's College London, London SE1 9RT, UK. e-mail: [email protected]Search for more papers by this author First published: 08 May 2015 https://doi.org/10.1111/bju.13177Read 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 No abstract is available for this article. Volume116, Issue3September 2015Pages 466-467 RelatedInformation

Comparative analysis of the Mycoplasma capricolum subsp. capricolum GM508D genome reveals subrogation of phase-variable contingency genes and a novel integrated genetic element.

Mycoplasma capricolum subspecies capricolum is both a pathogen of small ruminants and a model recipient organism for gene transplantation and synthetic biology. With the availability of the complete genome of the type strain California kid (released in 2005), a draft genome of strain GM508D was determined to investigate genomic variation in this subspecies. Differences in mobile genetic element location and complement, catabolic pathway genes, contingency loci, surface antigen genes and type II restriction-modification systems highlight the plasticity and diversity within this taxon.

Wanted: Prospective Studies of Alternative Donors

Wanted: Prospective Studies of Alternative Donors

Tissue typing and its role in transplantation

Transplantation of organ and haematopoietic stem cells is an established medical therapy, and success is dependent on finding the right donor bearing the appropriate human leucocyte antigen typing consisting mainly of class I (HLA‐A, HLA‐B and HLA‐C) and class II (class DP, DR and DQ) genes. These molecules engage with peptide fragments resulting in a complex interaction with dendritic cells and T cells. This plays an integral part in immune surveillance and modulates the recognition between self and nonself antigens. The principle of transplant biology is that any HLA disparity between donor and recipient triggers an ‘alloreactive response’ primarily mediated by T cells. This can result in graft‐versus‐host disease or graft‐versus‐leukaemia effect and has a significant role in graft rejection. Historically, HLA typing was performed via serological methods, but the advent of molecular techniques including DNA sequencing has allowed for higher resolution typing resulting in improvements in survival. This has historically been across 6 alleles (HLA‐A, HLA‐B and HLA‐DR) but has recently been expanded to include HLA‐C and HLA‐DQ. Consistent data have demonstrated the superiority in transplantation success with a 10/10 HLA‐matched donor. The stringent HLA matching in allogeneic stem cell transplantation (SCT) requires a careful selection of unrelated donors and may be more difficult for ethnic minority patients. To circumvent this, novel methods have been developed including alternative conditioning regimens, T‐cell depletion and haplo‐identical/mismatched transplants. The pioneering use of cord blood as a donor source has enabled transplants to be performed despite some degree of HLA mismatching.

Specific calcineurin isoforms are involved in Drosophila toll immune signaling.

Because excessive or inadequate responses can be detrimental, immune responses to infection require appropriate regulation. Networks of signaling pathways establish versatility of immune responses. Drosophila melanogaster is a powerful model organism for dissecting conserved innate immune responses to infection. For example, the Toll pathway, which promotes activation of NF-κB transcription factors Dorsal/Dorsal-related immune factor (Dif), was first identified in Drosophila. Together with the IMD pathway, acting upstream of NF-κB transcription factor Relish, these pathways constitute a central immune signaling network. Inputs in these pathways contribute to specific and appropriate responses to microbial insults. Relish activity during infection is modulated by Ca(2+)-dependent serine/threonine phosphatase calcineurin, an important target of immunosuppressants in transplantation biology. Only one of the three Drosophila calcineurin isoforms, calcineurin A1, acts on Relish during infection. However, it is not known whether there is a role for calcineurin in Dorsal/Dif immune signaling. In this article, we demonstrate involvement of specific calcineurin isoforms, protein phosphatase at 14D (Pp2B-14D)/calcineurin A at 14F (CanA-14F), in Toll-mediated immune signaling. These isoforms do not affect IMD signaling. In cell culture, pharmacological inhibition of calcineurin or RNA interference against homologous calcineurin isoforms Pp2B-14D/CanA-14F, but not against isoform calcineurin A1, decreased Toll-dependent Dorsal/Dif activity. A Pp2B-14D gain-of-function transgene promoted Dorsal nuclear translocation and Dorsal/Dif activity. In vivo, Pp2B-14D/CanA-14F RNA interference attenuated the Dorsal/Dif-dependent response to infection without affecting the Relish-dependent response. Altogether, these data identify a novel input, calcineurin, in Toll immune signaling and demonstrate involvement of specific calcineurin isoforms in Drosophila NF-κB signaling.

Complement Interception Across Humoral Incompatibility in Solid Organ Transplantation: A Clinical Perspective.

The humoral barrier in transplant biology is the result of preformed donor-specific antibodies (DSAs), directed either against human leukocyte antigens (HLA) or non-HLA antigens such as blood group (ABO) molecules. The term "sensitization" applies to patients carrying these antibodies. Transplantation is widely accepted as a life-saving opportunity for patients with terminal end-organ disease. However, in sensitized patients, transplant outcome is hampered by antibody-mediated rejection (AMR) as a consequence of DSA exposure. Furthermore, sensitized patients have limited access to "matched" organs from the both living and deceased donor pool.Considering the crucial role of the complement system in the pathophysiology of AMR and the availability of complement intervention therapeutics, there is a growing interest in complement-targeting strategies. This review highlights the emerging importance of monitoring and modulation of the complement system in the context of enabling transplantation across humoral incompatibility in sensitized recipients with preformed anti-HLA or natural anti-ABO antibodies. It also discusses the significance of the complement system in the induction of accommodation and further emphasizes current and future perspectives of novel complement therapeutics.

Fungal infections in renal transplant patients.

Organ transplantation has always been considered to be the standard therapeutic interventions in patients with end-stage organ failure. In 2008, more than 29,000 organ transplants were performed in US. Survival rates among transplant recipients have greatly improved due to better understanding of transplant biology and more effective immunosuppressive agents. After transplant, the extent of the immune response is influenced by the amount of interleukin 2 (IL-2) being produced by the T-helper cells. Transplant immunosuppressive therapy primarily targets T cell-mediated graft rejection. Calcineurin inhibitor, which includes cyclosporine, pimecrolimus and tacrolimus, impairs calcineurin-induced up-regulation of IL-2 expression, resulting in increased susceptibility to invasive fungal diseases. This immunosuppressive state allows infectious complication, leading to a high mortality rate. Currently, overall mortality due to invasive fungal infections (IFIs) in solid organ transplant recipients ranges between 25% and 80%. The risk of IFI following renal transplant is associated with the dosage of immunosuppressive agents given, environmental factors and post-transplant duration. Most fungal infections occur in the first 6 months after transplant because of the use of numerous immunosuppressors. Candida spp. and Cryptococcus spp. are the yeasts most frequently isolated, while most frequent filamentous fungi (molds) isolated are Aspergillus spp. The symptoms of systemic fungal infections are non-specific and early detection of fungal infections and proper therapy are important in improving survival and reducing mortality. This article will provide an insight on the risk factors and clinical presentation, compare variation in treatment of IFIs in renal transplant patients, and evaluate the role of prophylactic therapy in this group of patients. We also report the course and management of two renal transplant recipients admitted to Staten Island University Hospital, both of whom developed pulmonary complications secondary to Aspergillus infection.

Fluorescent magnetic iron oxide nanoparticles for cardiac precursor cell selection from stromal vascular fraction and optimization for magnetic resonance imaging.

Fluorescent magnetic iron oxide nanoparticles have been used to label cells for imaging as well as for therapeutic purposes. The purpose of this study was to modify the approach to develop a nanoprobe for cell selection and imaging with a direct therapeutic translational focus. The approach involves physical coincubation and adsorption of superparamagnetic iron oxide nanoparticle-polyethylene glycol (SPION-PEG) complexes with a monoclonal antibody (mAb) or a set of antibodies. Flow cytometry, confocal laser scanning microscopy, transmission electron microscopy, iron staining, and magnetic resonance imaging were used to assess cell viability, function, and labeling efficiency. This process has been validated by selecting adipose tissue-derived cardiac progenitor cells from the stromal vascular fraction using signal regulatory protein alpha (SIRPA)/kinase domain receptor (KDR) mAbs. These markers were chosen because of their sustained expression during cardiomyocyte differentiation. Sorting of cells positive for SIRPA and KDR allowed the enrichment of cardiac progenitors with 90% troponin-I positivity in differentiation cultures. SPION labeled cardiac progenitor cells (1×105 cells) was mixed with gel and used for 3T magnetic resonance imaging at a concentration, as low as 12.5 μg of iron. The toxicity assays, at cellular and molecular levels, did not show any detrimental effects of SPION. Our study has the potential to achieve moderate to high specific cell selection for the dual purpose of imaging and therapy.

Selected reviews from the 2015 BMT tandem meetings.

Before 2013, the American Society of Blood and Marrow Transplantation (ASBMT) organized a comprehensive education supplement published in Biology of Blood and Marrow Transplantation in conjunction with the annual BMT Tandem Meetings, jointly organized by the ASBMT and the Center for International Blood and Marrow Transplant Research (CIBMTR). Beginning with last year’s meeting, the education supplement was condensed to comprise critical reviews of 3 topics, selected by the meeting co-chairs, highlighting topics of particular interest. This year we are pleased to present 3 outstanding review articles compiled by scientific session speakers who are world leaders in their respective disciplines that examine topics of broad interest to the transplant community. In the first review, Drs. Paresh Vyas, Frederick Appelbaum, and Charles Craddock review the current state of allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML). AML remains the leading indication for allogeneic HCT in the world, with over 25,000 patients transplanted for this indication in the 10-year span from 2001 to 2011 (source: CIBMTR, 2014). As discussed by the authors, AML presents both opportunity and persistent challenge, given the clear importance of the graft-versusleukemia response seen after HCT as well as the fact that the most common cause of death in treated patients remains therapy-resistant disease. In this collaborative review, Dr. Vyas first presents an overviewof leukemiabiology.Hedescribesour rapidevolution from a conventional strategy of AML diagnosis and prognostic assessment based onmorphologic and cytogenetic evaluation that guided decisions about transplantation for decades. He discusses the expanding use of molecular studies, including emerging studies based on whole genome and exome sequencing in newly diagnosed AML patients. He also discusses the important role of clonal heterogeneity within the leukemic population, including the putative role of leukemic stem cells in leukemia persistence and treatment failure.

Radioimmunotherapy in Allogeneic Nonmyeloablative Conditioning for B Cell Lymphoma: Should We Use It More Often?

In this issue of Biology of Blood and Marrow Transplantation, Cassaday and coworkers reported improved survival rates in patients with indolent B-cell lymphomas who underwent anti-CD-20 radioimmunotherapy using yttrium-90-ibrutinib tiuxetan (90YIT) with their nonmyeloablative transplant conditioning regimen.1 All these patients had been exposed to rituximab. The authors compared their results to those of a historical control group of patients who did not receive 90YIT.1 After adjusting for imbalances in patients’ characteristics including chemoresistant and bulky disease, thrombocytopenia and Hematopoietic Cell Transplant Comorbidity Index Scores of ≥ 3, favoring the control group, the 3-year adjusted estimates of overall survival and progression-free survival in the 90YIT were 87% and 71%, vs 59% and 44% in the non-90YIT group. The authors acknowledge the limitation of the small number of patients studied (n=18), which was even smaller after adjusting for high-risk disease features described above. Nevertheless, their findings further confirm that RIT improves the outcome of patients with relapsed or refractory high-risk indolent lymphoma who have been considered for nonmyeloablative allogeneic transplantation. They are also in agreement with those of an earlier report from our center of a 3-year progression-free survival rate of 80% in refractory follicular lymphoma patients after allogeneic transplantation and 90YIT.2 Nonmyeloablative conditioning has been the cornerstone of adoptive allogeneic immunotherapy for B-cell indolent lymphoma that has failed to respond to conventional treatment. Pre-transplantation chemosensitivity vs refractoriness has been an important determinant of outcomes,3 and how to treat refractory disease without inducing additional toxicity has been a challenge. One strategy to enhance initial disease control is to incorporate novel agents into allogeneic conditioning regimens that are effective against lymphoma; remission can later be sustained via the graft-versus-lymphoma effect. One of the most compelling of these agents is 90YIT, which is used as targeted therapy in indolent lymphomas. The known sensitivity of B-cell indolent lymphomas to conventional radiotherapy makes them an attractive target for RIT. In the United States, 90YIT (Zevalin; Spectrum Pharmaceuticals, Henderson, NV) has been approved for the treatment of relapsed low-grade and follicular lymphomas. In 2009, the drug received an additional indication for use as consolidation after initial chemotherapy.4 90YIT uses the antibody to mediate complement-mediated cytotoxicity, along with the delivery of high-energy, short path-length (5 mm) beta irradiation from 90Y to both CD20-lymphoma cells and neighboring tumor cells that are inaccessible to the antibody or have insufficient antigen expression as a result of a cross-fire effect, with little effect on other solid organs. Of note, positive results were found in this study in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (10 of 18 patients), while the degree of marrow involvement and cytopenia were not factored into eligibility criteria to receive 90YIT. RIT is not known to be active as a single agent, without transplantation, in these histologic types. In a study at MD Anderson, 90YIT was administered to 14 patients with relapsed CLL that was in partial (but with 100,000/mm3. Of the 13 patients evaluable for response, only 1 patient achieved an MRD-negative remission but soon thereafter had Richter transformation. Grade ≥ 3 hematological toxicity was seen in 12 of the 13 evaluable patients. In view of this contrast in responses and safety, further exploration is needed of the mechanism of action of 90YIT in these diseases in the context of allogeneic transplantation. How can the information in the Cassaday et al study be used in clinical practice? The results of the current study confirm that the type of conditioning used in nonmyeloablative transplantation strategies matters and that one size does not fit all. The results of this study and the study at our center suggest that 90YIT should be more frequently administered to patients with active or refractory indolent lymphoma before transplantation. However, patients should be treated in clinical trials. The CLL results are intriguing and need to be confirmed in other studies. Contrary to previous findings in mouse models,6 it appears that prior exposure to rituximab does not affect the efficacy or safety of transplantation with 90YIT. Finally, this study does not address the lingering question in allogeneic transplantation: the incidence of graft-versus-host disease (GVHD). Over 70% of patients in this study developed acute II-IV GVHD. This incidence appears to be higher (23%) than the one observed in our transplantation study with 90YIT,2 suggesting that the difference is related to the GVHD prophylaxis used rather than to the innate conditioning regimen. In this era of novel B-cell receptor pathway-targeted agents such as ibrutinib and idelalisib, it is paramount that the safety of allogeneic transplantation be enhanced to encourage referrals from the community.

Xenotransplantation of porcine islet cells as a potential option for the treatment of type 1 diabetes in the future.

Solid organ and cell transplantation, including pancreatic islets constitute the treatment of choice for chronic terminal diseases. However, the clinical use of allogeneic transplantation is limited by the growing shortage of human organs. This has prompted us to initiate a unique multi-center and multi-team effort to promote translational research in xenotransplantation to bring xenotransplantation to the clinical setting. Supported by the German Research Foundation, an interdisciplinary group of surgeons, internal medicine doctors, diabetologists, material sciences experts, immunologists, cell biologists, virologists, veterinarians, and geneticists have established a collaborative research center (CRC) focusing on the biology of xenogeneic cell, tissue, and organ transplantation. A major strength of this consortium is the inclusion of members of the regulatory bodies, including the Paul-Ehrlich Institute (PEI), infection specialists from the Robert Koch Institute and PEI, veterinarians from the German Primate Center, and representatives of influential ethical and religious institutions. A major goal of this consortium is to promote islet xenotransplantation, based on the extensive expertise and experience of the existing clinical islet transplantation program. Besides comprehensive approaches to understand and prevent inflammation-mediated islet xenotransplant dysfunction [immediate blood-mediated inflammatory reaction (IBMIR)], we also take advantage of the availability of and experience with islet macroencapsulation, with the goal to improve graft survival and function. This consortium harbors a unique group of scientists with complementary expertise under a cohesive program aiming at developing new therapeutic approaches for islet replacement and solid organ xenotransplantation.

Regenerative Medicine Applications in Organ Transplantation

The rapidly evolving field of Regenerative Medicine is paving the way to unprecedented therapeutic opportunities, with several novel applications already being tested in the clinical settings. The book “Regenerative Medicine Applications in Organ Transplantation” edited by Drs. Orlando, Lerut, Soker, and Stratta offers an authoritative and timely overview of the ongoing progress and applicative potential of regenerative medicine for the treatment of end-stage organ failure. Notably, the editors should be commended for having succeeded in assembling an outstanding multidisciplinary roster of international experts involved with basic, translational, and clinical research endeavors. The end result is a comprehensive account of the evolution and the state-of-the-art of transplant biology and regenerative medicine, which highlights the intertwined relationship existing between these fields. Excellent color images and diagrams enrich each chapter, contributing to their clarity. The book represents an invaluable reference for students, physicians, and researchers who are interested in getting a comprehensive up-to-date snapshot on how regenerative medicine and organ transplantation are reshaping the medical profession. “Regenerative Medicine Applications in Organ Transplantation,” First edition, edited by Giuseppe Orlando, Jan P. Lerut, Shay Soker and Robert J. Stratta (1,011 pages), published in 2014 by Academic Press, Elsevier (ISBN: 978-0-12-398523-1). Price: U.S. $250.00.Figure

生体質感造形 Bio-Texture Modeling による触感等価立体臓器組織モデリングと臓器移植保存シミュレーション

生体質感造形 Bio-Texture Modeling による触感等価立体臓器組織モデリングと臓器移植保存シミュレーション

Editorial introductions

Current Opinion in Hematology was launched in 1994. 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 hematology is divided into nine 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 Andrea BacigalupoAndrea BacigalupoDr Bacigalupo is the Head of the Division of Hematology and Stem Cell Transplants at Ospedale San Martino, Genova, Italy. He graduated in 1973 from the Genova Medical School, Italy, and started an allogeneic transplant program in 1976. He has conducted several clinical trials in patients with aplastic anemia and in patients undergoing allogeneic transplants. His main interests are bone marrow failure, Graft-versus-Host-Disease (GvHD) and related complications, and graft versus leukemia reactions. He has also been interested in cytomegalovirus and Epstein–Barr virus infections, looking at early diagnosis and prospective studies on prophylaxis and pre-emptive therapy. Dr Bacigalupo has served as a board member of the European Group for Bone Marrow Transplantation (EBMT) for several years, as secretary, then Chairperson of the Aplastic Anemia Working Party and then as President from 1998 to 2002. He served as President of the Italian Group of Bone Marrow Transplantation (GITMO) from 2002 to 2005. He has been a member of the Italian National Health Council for two terms (2000–2006). He has served on the Regimen Related Toxicity Working Group of the Center for International Blood and Marrow Transplant Research (CIBMTR). Dr Bacigalupo has published over 500 articles in peer-reviewed journals and he is a member of several national and international hematology societies. He is Associate Editor of the journal Bone Marrow Transplantation and Biology of Blood and Marrow Transplantation. He serves on the Board of Haematologica and of the Journal of Clinical Oncology. Jed B. GorlinJed B. GorlinA leading authority in transfusion medicine, Dr Jed Gorlin oversees Quality and Regulatory Affairs, Training and Education, and Physician Services at Memorial Blood Centers/Innovative Blood Resources, USA. He provides medical education and transfusion support to hospital partners, and carries the organization's mission and expertise to national and international blood centers, as well as prospective hospital and laboratory clients. He has served on the boards of the AABB and National Blood Foundation, is Director of Transfusion Medicine at Hennepin County Medical Center, USA, and consults with the Minnesota Department of Health. Dr Gorlin has been a consultant to AABB-PEPFAR (President's Emergency Plan for AIDS Relief) projects in Rwanda and Tanzania. He has presented on transfusion preparedness and infectious disease screening at many blood centers in China. He has provided technical assistance for transfusion medicine projects in Kabul, Afghanistan, Kazakhstan and Kyrgyzstan. He is a technical consultant for transfusion response to obstetric hemorrhage to several groups working to reduce the frequency of maternal mortality including, the California Maternal Quality Care Collaborative, the American Congress of Obstetricians and Gynecologists and the Association of Women's Health, Obstetric and Neonatal Nurses (AWHONN). The AWHONN has a project funded by Merck for mothers, which has pilot projects to reduce maternal mortality from hemorrhage in New Jersey, Georgia and Washington, DC. Prior to joining Memorial Blood Centers in 1997, Dr Gorlin was acting medical director for transfusion services at Children's Hospital in Boston, USA, and for nearly 10 years held various positions at Children's Hospital and the Dana-Farber Cancer Institute, USA, a principal teaching affiliate of Harvard Medical School, USA. Board certified in pediatrics, and blood banking and transfusion medicine, he received his undergraduate degree from Stanford University, USA, a doctor of medicine degree from Yale University, USA, and a M.B.A. from the University of Minnesota's Carlson School of Business, USA.

Genetic polymorphisms and kidney transplant outcomes.

Gene polymorphism studies are growing at a quasiexponential rate and aim to improve immediate and long-term outcomes in renal transplantation. This review highlights recent evidence and potential future directions for genetic research studies. Studies are largely based on immunity, inflammation and pharmacogenetics, investigating mostly 'surrogate' outcomes with sometimes conflicting results. However, the last 12 months has also heralded the emergence of important genome-wide association studies on transplantation, more robust replicated multicentre analyses of candidate gene variants, meta-analyses, and an increasing interest in copy number variation and donor genetics. These studies set the scene for further investigation, aiming to understand pathways of disease and biomarkers of risk, and are leading to a greater understanding of the biology of transplantation. Future studies will require focus on donor : recipient and gene : environment interactions, and an integrated approach of 'transplantomics' to evaluate long-term outcomes in multinational collaborations.

Cloning and bioinformatics analysis of a full-length cDNA of porcine CR1-like gene.

Jing Cheng1, Junbing Jiang1, Junxing Zhao1, Zhirui Wang2,3, Yaogui Sun1, Haili Ma1, Kuohai Fan1, Wei Yin1, Na Sun1, Zhiwei Wang1, Xin Zhao1, and Hongquan Li1* College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02148, USA MGH-DF/HCC Recombinant Protein Expression and Purification Core, Boston, MA 02148, USA *Correspondence address. Tel/Fax: þ86-354-6288409; E-mail: livets@163.com

Bone marrow and peripheral blood stem cell transplant: a bioinformatics approach for mismatched donor recipient pairs.

Bone marrow and peripheral blood stem cell transplants when performed outside the family require high resolution matching of donor and recipient for human leukocyte antigen loci. Marrow registries like National Marrow Development Program in developed countries maintain record of donors and provide most suitable donor when a recipient needs a transplant. Being outside families and due to lack of shared haplotypes, these are not fully matched. Depending upon condition of patient and time available, several times one or two loci mismatched marrow has to be transplanted. This matching can be further enhanced by introduction of a recently introduced branch of science known as Bioinformatics. Combining the knowledge of computer softwares and transplant biology, it is possible to place any protein (in this case specific human leukocyte antigen alleles of potential donors and recipient) against any other, for exact amino-acids match/mismatch in user defined region and thus choosing the better-matched donor. In this write-up, an introduction of few programs available that can be used for the said purpose is given with a brief discussion of approach already used by other scientists.

The chicken chorioallantoic membrane model in biology, medicine and bioengineering.

The chicken chorioallantoic membrane (CAM) is a simple, highly vascularized extraembryonic membrane, which performs multiple functions during embryonic development, including but not restricted to gas exchange. Over the last two decades, interest in the CAM as a robust experimental platform to study blood vessels has been shared by specialists working in bioengineering, development, morphology, biochemistry, transplant biology, cancer research and drug development. The tissue composition and accessibility of the CAM for experimental manipulation, makes it an attractive preclinical in vivo model for drug screening and/or for studies of vascular growth. In this article we provide a detailed review of the use of the CAM to study vascular biology and response of blood vessels to a variety of agonists. We also present distinct cultivation protocols discussing their advantages and limitations and provide a summarized update on the use of the CAM in vascular imaging, drug delivery, pharmacokinetics and toxicology.