The Experts below are selected from a list of 21660 Experts worldwide ranked by ideXlab platform
Joachim Denner - One of the best experts on this subject based on the ideXlab platform.
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The porcine virome and Xenotransplantation
Virology Journal, 2017Co-Authors: Joachim DennerAbstract:The composition of the porcine virome includes viruses that infect pig cells, ancient virus-derived elements including endogenous retroviruses inserted in the pig chromosomes, and bacteriophages that infect a broad array of bacteria that inhabit pigs. Viruses infecting pigs, among them viruses also infecting human cells, as well as porcine endogenous retroviruses (PERVs) are of importance when evaluating the virus safety of Xenotransplantation. Bacteriophages associated with bacteria mainly in the gut are not relevant in this context. Xenotransplantation using pig cells, tissues or organs is under development in order to alleviate the shortage of human transplants. Here for the first time published data describing the viromes in different pigs and their relevance for the virus safety of Xenotransplantation is analysed. In conclusion, the analysis of the porcine virome has resulted in numerous new viruses being described, although their impact on Xenotransplantation is unclear. Most importantly, viruses with known or suspected zoonotic potential were often not detected by next generation sequencing, but were revealed by more sensitive methods.
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regulation of clinical Xenotransplantation time for a reappraisal
Transplantation, 2017Co-Authors: David K. C. Cooper, Muhammad M. Mohiuddin, Joachim Denner, Jay A Fishman, Richard N Pierson, Bernhard J Hering, Curie Ahn, Agnes M Azimzadeh, L Buhler, Peter J CowanAbstract:The continual critical shortage of organs and cells from deceased human donors has stimulated research in the field of cross-species transplantation (Xenotransplantation), with the pig selected as the most suitable potential source of organs. Since the US Food and Drug Administration concluded a comprehensive review of Xenotransplantation in 2003, considerable progress has been made in the experimental laboratory to improve cell and organ xenograft survival in several pig-to-nonhuman primate systems that offer the best available models to predict clinical outcomes. Survival of heart, kidney, and islet grafts in nonhuman primates is now being measured in months or even years. The potential risks associated with Xenotransplantation, for example, the transfer of an infectious microorganism, that were highlighted in the 2003 Food and Drug Administration guidance and subsequent World Health Organization consensus documents have been carefully studied and shown to be either less likely than previously thought or readily manageable by donor selection or recipient management strategies. In this context, we suggest that the national regulatory authorities worldwide should re-examine their guidelines and regulations regarding Xenotransplantation, so as to better enable design and conduct of safe and informative clinical trials of cell and organ Xenotransplantation when and as supported by the preclinical data. We identify specific topics that we suggest require reconsideration.
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first update of the international Xenotransplantation association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes executive summary
Xenotransplantation, 2016Co-Authors: Bernhard J Hering, David K. C. Cooper, Emanuele Cozzi, Thomas Spizzo, Peter J Cowan, Gina R Rayat, Joachim DennerAbstract:The International Xenotransplantation Association has updated its original "Consensus Statement on Conditions for Undertaking Clinical Trials of Porcine Islet Products in Type 1 Diabetes," which was published in Xenotransplantation in 2009. This update is timely and important in light of scientific progress and changes in the regulatory framework pertinent to islet Xenotransplantation. Except for the chapter on "informed consent," which has remained relevant in its 2009 version, all other chapters included in the initial consensus statement have been revised for inclusion in this update. These chapters will not provide complete revisions of the original chapters; rather, they restate the key points made in 2009, emphasize new and under-appreciated topics not fully addressed in 2009, suggest relevant revisions, and communicate opinions that complement the consensus opinion. Chapter 1 provides an update on national regulatory frameworks addressing Xenotransplantation. Chapter 2 a, previously Chapter 2, suggests several important revisions regarding the generation of suitable source pigs from the perspective of the prevention of xenozoonoses. The newly added Chapter 2b discusses conditions for the use of genetically modified source pigs in clinical islet Xenotransplantation. Chapter 3 reviews porcine islet product manufacturing and release testing. Chapter 4 revisits the critically important topic of preclinical efficacy and safety data required to justify a clinical trial. The main achievements in the field of transmission of all porcine microorganisms, the rationale for more proportionate recipient monitoring, and response plans are reviewed in Chapter 5. Patient selection criteria and circumstances where trials of islet Xenotransplantation would be both medically and ethically justified are examined in Chapter 6 in the context of recent advances in available and emerging alternative therapies for serious and potentially life-threatening complications of diabetes. It is hoped that this first update of the International Xenotransplantation Association porcine islet transplant consensus statement will assist the islet xenotransplant scientific community, sponsors, regulators, and other stakeholders actively involved in the clinical translation of islet Xenotransplantation.
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infection barriers to successful Xenotransplantation focusing on porcine endogenous retroviruses
Clinical Microbiology Reviews, 2012Co-Authors: Joachim Denner, Ralf R TonjesAbstract:SUMMARY Xenotransplantation may be a solution to overcome the shortage of organs for the treatment of patients with organ failure, but it may be associated with the transmission of porcine microorganisms and the development of xenozoonoses. Whereas most microorganisms may be eliminated by pathogen-free breeding of the donor animals, porcine endogenous retroviruses (PERVs) cannot be eliminated, since these are integrated into the genomes of all pigs. Human-tropic PERV-A and -B are present in all pigs and are able to infect human cells. Infection of ecotropic PERV-C is limited to pig cells. PERVs may adapt to host cells by varying the number of LTR-binding transcription factor binding sites. Like all retroviruses, they may induce tumors and/or immunodeficiencies. To date, all experimental, preclinical, and clinical Xenotransplantations using pig cells, tissues, and organs have not shown transmission of PERV. Highly sensitive and specific methods have been developed to analyze the PERV status of donor pigs and to monitor recipients for PERV infection. Strategies have been developed to prevent PERV transmission, including selection of PERV-C-negative, low-producer pigs, generation of an effective vaccine, selection of effective antiretrovirals, and generation of animals transgenic for a PERV-specific short hairpin RNA inhibiting PERV expression by RNA interference.
David K. C. Cooper - One of the best experts on this subject based on the ideXlab platform.
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the potential role of 3d bioprinting in Xenotransplantation
Current Opinion in Organ Transplantation, 2019Co-Authors: Wenjun Zhang, David K. C. Cooper, David Ayares, Lester J Smith, Burcin EkserAbstract:Purpose of reviewTo review the impact of a new technology, 3D-bioprinting, in Xenotransplantation research.Recent findingsGenetically engineered pigs, beginning with human (h) CD55-transgenic and Gal-knockout pigs, have improved the outcomes of Xenotransplantation research. Today, there are more tha
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the case for cardiac Xenotransplantation in neonates is now the time to reconsider Xenotransplantation for hypoplastic left heart syndrome
Pediatric Cardiology, 2019Co-Authors: David C Cleveland, Hidetaka Hara, Adam C Banks, Waldemar F Carlo, David C Mauchley, David K. C. CooperAbstract:Neonatal cardiac transplantation for hypoplastic left heart syndrome (HLHS) is associated with excellent long-term survival compared to older recipients. However, heart transplantation for neonates is greatly limited by the critical shortage of donor hearts, and by the associated mortality of the long pre-transplant waiting period. This led to the development of staged surgical palliation as the first-line surgical therapy for HLHS. Recent advances in genetic engineering and Xenotransplantation have provided the potential to replicate the excellent results of neonatal cardiac allotransplantation while eliminating wait-list-associated mortality through genetically modified pig-to-human neonatal cardiac Xenotransplantation. The elimination of the major pig antigens in addition to the immature B-cell response in neonates allows for the potential to induce B-cell tolerance. Additionally, the relatively mature neonatal T-cell response could be reduced by thymectomy at the time of operation combined with donor-specific pig thymus transplantation to “reprogram” the host’s T-cells to recognize the xenograft as host tissue. In light of the recent significantly increased graft survival of genetically-engineered pig-to-baboon cardiac Xenotransplantation, we propose that now is the time to consider devoting research to advance the potential clinical application of cardiac Xenotransplantation as a treatment option for patients with HLHS. Employing cardiac Xenotransplantation could revolutionize therapy for complex congenital heart defects and open a new chapter in the field of pediatric cardiac transplantation.
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the role of costimulation blockade in solid organ and islet Xenotransplantation
Clinical & Developmental Immunology, 2017Co-Authors: Kannan P Samy, David K. C. Cooper, James R Butler, Burcin EkserAbstract:Pig-to-human Xenotransplantation offers a potential bridge to the growing disparity between patients with end-stage organ failure and graft availability. Early studies attempting to overcome cross-species barriers demonstrated robust humoral immune responses to discordant xenoantigens. Recent advances have led to highly efficient and targeted genomic editing, drastically altering the playing field towards rapid production of less immunogenic porcine tissues and even the discussion of human Xenotransplantation trials. However, as these humoral immune barriers to cross-species transplantation are overcome with advanced transgenics, cellular immunity to these novel xenografts remains an outstanding issue. Therefore, understanding and optimizing immunomodulation will be paramount for successful clinical Xenotransplantation. Costimulation blockade agents have been introduced in Xenotransplantation research in 2000 with anti-CD154mAb. Most recently, prolonged survival has been achieved in solid organ (kidney xenograft survival > 400 days with anti-CD154mAb, heart xenograft survival > 900 days, and liver xenograft survival 29 days with anti-CD40mAb) and islet Xenotransplantation (>600 days with anti-CD154mAb) with the use of these potent experimental agents. As the development of novel genetic modifications and costimulation blocking agents converges, we review their impact thus far on preclinical Xenotransplantation and the potential for future application.
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regulation of clinical Xenotransplantation time for a reappraisal
Transplantation, 2017Co-Authors: David K. C. Cooper, Muhammad M. Mohiuddin, Joachim Denner, Jay A Fishman, Richard N Pierson, Bernhard J Hering, Curie Ahn, Agnes M Azimzadeh, L Buhler, Peter J CowanAbstract:The continual critical shortage of organs and cells from deceased human donors has stimulated research in the field of cross-species transplantation (Xenotransplantation), with the pig selected as the most suitable potential source of organs. Since the US Food and Drug Administration concluded a comprehensive review of Xenotransplantation in 2003, considerable progress has been made in the experimental laboratory to improve cell and organ xenograft survival in several pig-to-nonhuman primate systems that offer the best available models to predict clinical outcomes. Survival of heart, kidney, and islet grafts in nonhuman primates is now being measured in months or even years. The potential risks associated with Xenotransplantation, for example, the transfer of an infectious microorganism, that were highlighted in the 2003 Food and Drug Administration guidance and subsequent World Health Organization consensus documents have been carefully studied and shown to be either less likely than previously thought or readily manageable by donor selection or recipient management strategies. In this context, we suggest that the national regulatory authorities worldwide should re-examine their guidelines and regulations regarding Xenotransplantation, so as to better enable design and conduct of safe and informative clinical trials of cell and organ Xenotransplantation when and as supported by the preclinical data. We identify specific topics that we suggest require reconsideration.
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Xenotransplantation: past, present, and future.
Current opinion in organ transplantation, 2017Co-Authors: Burcin Ekser, David K. C. CooperAbstract:Purpose of review To review the progress in the field of Xenotransplantation with special attention to most recent encouraging findings which will eventually bring Xenotransplantation to the clinic in the near future. Recent findings Starting from early 2000, with the introduction of galactose-α1,3-galactose (Gal)-knockout pigs, prolonged survival especially in heart and kidney Xenotransplantation was recorded. However, remaining antibody barriers to non-Gal antigens continue to be the hurdle to overcome. The production of genetically engineered pigs was difficult requiring prolonged time. However, advances in gene editing, such as zinc finger nucleases, transcription activator-like effector nucleases, and most recently clustered regularly interspaced short palindromic repeats (CRISPR) technology made the production of genetically engineered pigs easier and available to more researchers. Today, the survival of pig-to-nonhuman primate heterotopic heart, kidney, and islet Xenotransplantation reached more than 900, more than 400, and more than 600 days, respectively. The availability of multiple-gene pigs (five or six genetic modifications) and/or newer costimulation blockade agents significantly contributed to this success. Now, the field is getting ready for clinical trials with an international consensus. Summary Clinical trials in cellular or solid organ Xenotransplantation are getting closer with convincing preclinical data from many centers. The next decade will show us new achievements and additional barriers in clinical Xenotransplantation.
Jeffrey L. Platt - One of the best experts on this subject based on the ideXlab platform.
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Pulmonary Xenotransplantation: rapidly progressing into the unknown.
American Journal of Transplantation, 2004Co-Authors: Edward Cantu, William Parker, Jeffrey L. Platt, R. Duane DavisAbstract:As one approach to circumventing the dire shortage of human lungs for transplantation, a handful of investigators have begun to probe the possibility of pulmonary Xenotransplantation. The immunologic and perhaps physiologic barriers encountered by these investigators are considerable and progress in pulmonary Xenotransplantation has lagged behind progress in cardiac and kidney Xenotransplantation. However, during the last few years there have been substantial advances in the field of pulmonary Xenotransplantation including, most noticeably, significant progress in attenuating hyperacute dysfunction. Progress has been made in understanding the barriers imposed by xenoreactive antibodies, complement, coagulation incompatibility and porcine pulmonary intravascular macrophages. Although our understanding of the barriers to pulmonary Xenotransplantation is far from complete and the clinical application of pulmonary Xenotransplantation is not yet in sight, current progress is fast paced. This progress provides a basis for future work and for a hope that the shortage of human lungs for transplantation will not always be a matter of life and death.
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Cardiac Xenotransplantation: future and limitations.
Cardiology, 2004Co-Authors: Kiyoshi Ogata, Jeffrey L. PlattAbstract:Despite improvements in pharmacological therapies, the outlook for patients with severe cardiac disease remains poor. At present, only transplantation can 'cure' end-stage cardiac failure. However, fewer than 5% of those who need a cardiac transplant receive one in the United States each year. To address this problem, some propose using animals as a source of organs for transplantation, that is, Xenotransplantation. Here, we discuss the rationale for Xenotransplantation beyond overcoming the shortage of human organs, and we weigh Xenotransplantation against other new technologies that might be used for the treatment of cardiac failure.
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Potential applications and prospects for cardiac Xenotransplantation
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 2004Co-Authors: Kiyoshi Ogata, Jeffrey L. PlattAbstract:Abstract Despite improvements in pharmacologic therapies, the outlook for patients with severe cardiac disease remains poor. At present, the only "cure" for end-stage heart failure is transplantation. However, fewer than 5% of those who need a cardiac transplant receive one in the United States each year. As an alternative, some propose using animals as a source of organs for transplantation (i.e., Xenotransplantation). In this article we review the potential applications of Xenotransplantation for the treatment of cardiac disease, and weigh Xenotransplantation against other new technologies that might be used. We also consider the current status of addressing the hurdles to application of Xenotransplantation.
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Pathological Responses to Xenotransplantation
2002Co-Authors: Matilde Bustos, Jeffrey L. PlattAbstract:The idea of transplanting animal organs into patients with organ failure is not new. When the development of vascular anastomosis made organ transplantation feasible from a surgical perspective, a few clinical renal xenografts were attempted. In 1906, Jaboulay (1) described the Xenotransplantation of pig and goat grafts into humans. Neither pig nor goat grafts functioned, and the failure of the xenograft did not allow vascular thrombosis to be observed. At the same time, Unger performed Xenotransplantation using organs from nonhuman primates with similar results (2). In 1923, Harol Neuhof affirmed that thrombosis or hemorrhage in the xenotransplant could be prevented (2). However, technical imperfection and the lack of understanding of immunological host reactivity led to waning interest in Xenotransplantation.
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Genetic therapies and Xenotransplantation.
Expert opinion on biological therapy, 2002Co-Authors: Brenda M. Ogle, Jeffrey L. PlattAbstract:The number of patients in need of an organ transplant is increasing, while the number of satisfactory sources of organs has declined in many countries [101]. The resulting shortage of human organs has spurred an urgent effort to investigate alternative therapies, including the use of animal organs, tissues and cells (i.e., Xenotransplantation). Advances in genetic engineering have provided essential tools for the development of practical solutions to human disease. The area of Xenotransplantation is no exception. In fact, the use of genetic therapies is especially attractive in the transplant setting as it offers an opportunity to manipulate the donor tissue rather than the recipient. This review will describe the obstacles in the clinical application of Xenotransplantation and how genetic engineering might be used to address them.
Robin A. Weiss - One of the best experts on this subject based on the ideXlab platform.
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Retroviruses and Xenotransplantation
Xenotransplantation, 2014Co-Authors: Robin A. WeissAbstract:Most vertebrate species harbor multiple inherited proviruses, which are called endogenous retroviruses (ERV) to distinguish them from infectiously transmitted, exogenous retroviruses. These inherited retroviruses in potential source animals raise questions about their potential transmission via Xenotransplantation and are discussed in this chapter. It is noteworthy that xenotropic retroviruses have been found to infect foreign cells in the Xenotransplantation setting. The possibility of recombination between animal retroviruses and endogenous or infectious human retroviral genomes needs to be borne in mind in Xenotransplantation. As pigs are a favored species for Xenotransplantation to humans, there has been renewed interest in porcine retroviruses. Unlike ruminants such as sheep, pigs appear to carry only one group of infectious retrovirus, the C-type retroviruses, related to murine leukemia virus (MLV) and gibbon ape leukemia virus (GALV). The foregoing discussion of natural and experimental infection across large phylogenetic distances and other factors, show that retroviruses are able to infect and cause disease in hosts wholly unrelated to those from which they emerge. Indeed, the zoonoses discussed in this chapter illustrate that animal retroviruses have found other means of infiltrating humans. Xenotransplantation can offer the extremely rare event of zoonosis much more opportunity to occur, for many reasons. First, the physical barrier to cross-species infection is breached by implanting animal tissues in humans. Second, the immunosuppression necessary to prevent graft rejection may allow the virus to take and propagate in the human body. More research is required on retroviral and other infections in relation to Xenotransplantation.
Burcin Ekser - One of the best experts on this subject based on the ideXlab platform.
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the potential role of 3d bioprinting in Xenotransplantation
Current Opinion in Organ Transplantation, 2019Co-Authors: Wenjun Zhang, David K. C. Cooper, David Ayares, Lester J Smith, Burcin EkserAbstract:Purpose of reviewTo review the impact of a new technology, 3D-bioprinting, in Xenotransplantation research.Recent findingsGenetically engineered pigs, beginning with human (h) CD55-transgenic and Gal-knockout pigs, have improved the outcomes of Xenotransplantation research. Today, there are more tha
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the role of costimulation blockade in solid organ and islet Xenotransplantation
Clinical & Developmental Immunology, 2017Co-Authors: Kannan P Samy, David K. C. Cooper, James R Butler, Burcin EkserAbstract:Pig-to-human Xenotransplantation offers a potential bridge to the growing disparity between patients with end-stage organ failure and graft availability. Early studies attempting to overcome cross-species barriers demonstrated robust humoral immune responses to discordant xenoantigens. Recent advances have led to highly efficient and targeted genomic editing, drastically altering the playing field towards rapid production of less immunogenic porcine tissues and even the discussion of human Xenotransplantation trials. However, as these humoral immune barriers to cross-species transplantation are overcome with advanced transgenics, cellular immunity to these novel xenografts remains an outstanding issue. Therefore, understanding and optimizing immunomodulation will be paramount for successful clinical Xenotransplantation. Costimulation blockade agents have been introduced in Xenotransplantation research in 2000 with anti-CD154mAb. Most recently, prolonged survival has been achieved in solid organ (kidney xenograft survival > 400 days with anti-CD154mAb, heart xenograft survival > 900 days, and liver xenograft survival 29 days with anti-CD40mAb) and islet Xenotransplantation (>600 days with anti-CD154mAb) with the use of these potent experimental agents. As the development of novel genetic modifications and costimulation blocking agents converges, we review their impact thus far on preclinical Xenotransplantation and the potential for future application.
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Xenotransplantation: past, present, and future.
Current opinion in organ transplantation, 2017Co-Authors: Burcin Ekser, David K. C. CooperAbstract:Purpose of review To review the progress in the field of Xenotransplantation with special attention to most recent encouraging findings which will eventually bring Xenotransplantation to the clinic in the near future. Recent findings Starting from early 2000, with the introduction of galactose-α1,3-galactose (Gal)-knockout pigs, prolonged survival especially in heart and kidney Xenotransplantation was recorded. However, remaining antibody barriers to non-Gal antigens continue to be the hurdle to overcome. The production of genetically engineered pigs was difficult requiring prolonged time. However, advances in gene editing, such as zinc finger nucleases, transcription activator-like effector nucleases, and most recently clustered regularly interspaced short palindromic repeats (CRISPR) technology made the production of genetically engineered pigs easier and available to more researchers. Today, the survival of pig-to-nonhuman primate heterotopic heart, kidney, and islet Xenotransplantation reached more than 900, more than 400, and more than 600 days, respectively. The availability of multiple-gene pigs (five or six genetic modifications) and/or newer costimulation blockade agents significantly contributed to this success. Now, the field is getting ready for clinical trials with an international consensus. Summary Clinical trials in cellular or solid organ Xenotransplantation are getting closer with convincing preclinical data from many centers. The next decade will show us new achievements and additional barriers in clinical Xenotransplantation.
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clinical lung Xenotransplantation what donor genetic modifications may be necessary
Xenotransplantation, 2012Co-Authors: David K. C. Cooper, Hidetaka Hara, Burcin Ekser, Christopher Burlak, Leela L. Paris, Agnes M Azimzadeh, Mohamed Ezzelarab, Joseph A Tector, Carol Phelps, David AyaresAbstract:Cooper DKC, Ekser B, Burlak C, Ezzelarab M, Hara H, Paris L, Tector AJ, Phelps C, Azimzadeh AM, Ayares D, Robson SC, Pierson RN III. Clinical lung Xenotransplantation – what donor genetic modifications may be necessary? Xenotransplantation 2012; 19: 144–158. © 2012 John Wiley & Sons A/S. Abstract: Barriers to successful lung Xenotransplantation appear to be even greater than for other organs. This difficulty may be related to several macro anatomic factors, such as the uniquely fragile lung parenchyma and associated blood supply that results in heightened vulnerability of graft function to segmental or lobar airway flooding caused by loss of vascular integrity (also applicable to allotransplants). There are also micro-anatomic considerations, such as the presence of large numbers of resident inflammatory cells, such as pulmonary intravascular macrophages and natural killer (NK) T cells, and the high levels of von Willebrand factor (vWF) associated with the microvasculature. We have considered what developments would be necessary to allow successful clinical lung Xenotransplantation. We suggest this will only be achieved by multiple genetic modifications of the organ-source pig, in particular to render the vasculature resistant to thrombosis. The major problems that require to be overcome are multiple and include (i) the innate immune response (antibody, complement, donor pulmonary and recipient macrophages, monocytes, neutrophils, and NK cells), (ii) the adaptive immune response (T and B cells), (iii) coagulation dysregulation, and (iv) an inflammatory response (e.g., TNF-α, IL-6, HMGB1, C-reactive protein). We propose that the genetic manipulation required to provide normal thromboregulation alone may include the introduction of genes for human thrombomodulin/endothelial protein C-receptor, and/or tissue factor pathway inhibitor, and/or CD39/CD73; the problem of pig vWF may also need to be addressed. It would appear that exploration of every available therapeutic path will be required if lung Xenotransplantation is to be successful. To initiate a clinical trial of lung Xenotransplantation, even as a bridge to allotransplantation (with a realistic possibility of survival long enough for a human lung allograft to be obtained), significant advances and much experimental work will be required. Nevertheless, with the steadily increasing developments in techniques of genetic engineering of pigs, we are optimistic that the goal of successful clinical lung Xenotransplantation can be achieved within the foreseeable future. The optimistic view would be that if experimental pig lung Xenotransplantation could be successfully managed, it is likely that clinical application of this and all other forms of Xenotransplantation would become more feasible.
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Immunobiology of liver Xenotransplantation
Expert review of clinical immunology, 2012Co-Authors: Burcin Ekser, Simon C Robson, Christopher Burlak, Joshua P. Waldman, Andrew J. Lutz, Leela L. Paris, Massimiliano Veroux, Michael A. Rees, David Ayares, Bruno GridelliAbstract:Pigs are currently the preferred species for future organ Xenotransplantation. With advances in the development of genetically modified pigs, clinical Xenotransplantation is becoming closer to reality. In preclinical studies (pig-to-nonhuman primate), the Xenotransplantation of livers from pigs transgenic for human CD55 or from α1,3-galactosyltransferase gene-knockout pigs+/– transgenic for human CD46, is associated with survival of approximately 7–9 days. Although hepatic function, including coagulation, has proved to be satisfactory, the immediate development of thrombocytopenia is very limiting for pig liver Xenotransplantation even as a ‘bridge’ to allotransplantation. Current studies are directed to understand the immunobiology of platelet activation, aggregation and phagocytosis, in particular the interaction between platelets and liver sinusoidal endothelial cells, hepatocytes and Kupffer cells, toward identifying interventions that may enable clinical application.
