David Ayares
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View article: Coordinated circulating and tissue-based T cell responses precede xenograft rejection
Coordinated circulating and tissue-based T cell responses precede xenograft rejection Open
Despite the life-saving successes of solid organ transplantation, the number of individuals needing organ transplant far exceeds the number of organs available for use each year. Porcine xenotransplantation, or the use of pig organs for tr…
View article: Characterizing the Immune Response in Pig-to-Human Heart Xenografts Using a Multimodal Diagnostic System
Characterizing the Immune Response in Pig-to-Human Heart Xenografts Using a Multimodal Diagnostic System Open
BACKGROUND: Porcine genome editing has revolutionized xenotransplantation, recently enabling the first pig-to-human heart xenotransplants. However, the xenoimmune response in heart xenografts remains largely unexplored. This study aimed to…
MOLECULAR AND GENETIC ANALYSIS OF HOMOLOGOUS RECOMBINATION AND DEOXYRIBONUCLEIC ACID REPAIR IN MAMMALIAN CELLS. Open
MOLECULAR AND GENETIC ANALYSIS OF HOMOLOGOUS RECOMBINATION AND DEOXYRIBONUCLEIC ACID REPAIR IN MAMMALIAN CELLS.
Genetically engineered pig heart transplantation in non-human primates Open
These data demonstrate that 10 GE cardiac xenografts have variable cardiac xenograft survival in NHP due to perhaps presence of 4th antigen and require further study. However, these 10GE organs may be suitable for clinical cardiac xenotran…
Ultrasound Assessment of Pleural Effusions After Orthotopic Pig‐to‐Baboon Cardiac Xenotransplantation Open
Background Pleural effusions develop frequently after cardiac surgery in humans. Lung ultrasound is an essential non‐invasive tool in the diagnosis and treatment of these effusions. Pleural effusions also develop regularly after preclinica…
Combination of Anti-CD40 and Anti-CD40L Antibodies as Co-Stimulation Blockade in Preclinical Cardiac Xenotransplantation Open
The blockade of the CD40/CD40L immune checkpoint is considered essential for cardiac xenotransplantation. However, it is still unclear which single antibody directed against CD40 or CD40L (CD154), or which combination of antibodies, is bet…
An Approach to Controlling Inflammation and Coagulation in Pig‐to‐Baboon Cardiac Xenotransplantation Open
Introduction Inflammatory responses and coagulation disorders are a relevant challenge for successful cardiac xenotransplantation on its way to the clinic. To cope with this, an effective and clinically practicable anti‐inflammatory and an…
The Endothelial Glycocalyx in Pig-to-Baboon Cardiac Xenotransplantation—First Insights Open
Cardiac xenotransplantation has seen remarkable success in recent years and is emerging as the most promising alternative to human cardiac allotransplantation. Despite these achievements, acute vascular rejection still presents a challenge…
Transthoracic echocardiography is a simple tool for size matching in cardiac xenotransplantation Open
Background Preoperative size matching is essential for both allogeneic and xenogeneic heart transplantation. In preclinical pig‐to‐baboon xenotransplantation experiments, porcine donor organs are usually matched to recipients by using indi…
View article: Physiological basis for xenotransplantation from genetically modified pigs to humans
Physiological basis for xenotransplantation from genetically modified pigs to humans Open
The collective efforts of scientists over multiple decades have led to advancements in molecular and cellular biology-based technologies including genetic engineering and animal cloning that are now being harnessed to enhance the suitabili…
View article: Novel factors potentially initiating acute antibody‐mediated rejection in pig kidney xenografts despite an efficient immunosuppressive regimen
Novel factors potentially initiating acute antibody‐mediated rejection in pig kidney xenografts despite an efficient immunosuppressive regimen Open
Antibody‐mediated rejection (AMR) is a common cause of graft failure after pig‐to‐nonhuman primate organ transplantation, even when the graft is from a pig with multiple genetic modifications. The specific factors that initiate AMR are oft…
View article: Pigs in Transplantation Research and Their Potential as Sources of Organs in Clinical Xenotransplantation
Pigs in Transplantation Research and Their Potential as Sources of Organs in Clinical Xenotransplantation Open
The pig has long been used as a research animal and has now gained importance as a potential source of organs for clinical xenotransplantation. When an organ from a wild-type (i.e., genetically unmodified) pig is transplanted into an immun…
Hemodynamics in pig‐to‐baboon heterotopic thoracic cardiac xenotransplantation: Recovery from perioperative cardiac xenograft dysfunction and impairment by cardiac overgrowth Open
Introduction Orthotopic cardiac xenotransplantation has seen notable improvement, leading to the first compassionate use in 2022. However, it remains challenging to define the clinical application of cardiac xenotransplantation, including …
View article: Update on the ethical, legal and technical challenges of translating xenotransplantation
Update on the ethical, legal and technical challenges of translating xenotransplantation Open
This manuscript reports on a landmark symposium on the ethical, legal and technical challenges of xenotransplantation in the UK. King’s College London, with endorsement from the British Transplantation Society (BTS), and the European Socie…
View article: In vitro and in vivo immune assessments of genetically‐engineered pig skin grafts in New World (squirrel) monkeys
In vitro and in vivo immune assessments of genetically‐engineered pig skin grafts in New World (squirrel) monkeys Open
Half a million patients in the USA alone require treatment for burns annually. Following an extensive burn, it may not be possible to provide sufficient autografts in a single setting. Genetic manipulations (GM) of pigs offer the possibili…
Expression of human thrombomodulin by GalTKO.hCD46 pigs modulates coagulation cascade activation by endothelial cells and during ex vivo lung perfusion with human blood Open
Thrombomodulin is important for the production of activated protein C (APC), a molecule with significant regulatory roles in coagulation and inflammation. To address known molecular incompatibilities between pig thrombomodulin and human th…
View article: Glycocalyx dynamics and the inflammatory response of genetically modified porcine endothelial cells
Glycocalyx dynamics and the inflammatory response of genetically modified porcine endothelial cells Open
Xenotransplantation is a promising approach to reduce organ shortage, while genetic modification of donor pigs has significantly decreased the immunogenic burden of xenotransplants, organ rejection is still a hurdle. Genetically modified p…
View article: Integrative Multi-omic Profiling of Two Human Decedents Receiving Pig Heart Xenografts Reveals Strong Perturbations in Early Immune-Cell and Cellular Metabolism Responses
Integrative Multi-omic Profiling of Two Human Decedents Receiving Pig Heart Xenografts Reveals Strong Perturbations in Early Immune-Cell and Cellular Metabolism Responses Open
Background Recent advances in xenotransplantation in living and decedent humans using pig xenografts have laid promising groundwork towards future emergency use and first in human trials. Major obstacles remain though, including a lack of …