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453 results on '"Hawthorne, Wayne"'

1. Santander Statement: Towards Global Convergence in Transplantation: Sufficiency, Transparency, and Oversight

Author

Adamec, Milos, Ahn, Curie, Albreht, Katarina, Almén, Helena, Al Obaidli, Ali Abdul Kareem, Anušić Juričić, Martina, Arrabal, Samuel, Ascher, Nancy, Ashkenazi, Tamar, Avendaño-Solá, Cristina, Avsec, Danica, Badenes, Rafael, Bal, Omer, Ballesté, Chloë, Barquero, Teresita, Be, Alicia, Beltrán, Mauricio, Bengochea, Milka, Beqo, Flutra, Berenguer, Marina, Berishvili, Ekaterina, Bokhorst, Arlinke, Boletis, Ioannis, Bolocan, Vladimir, Koh, Mickey BC, Börgel, Martin, Briceño, Javier, Brix-Zuleger, Martina, Busic, Mirela, Buziuviene, Audrone, Caballero, Xavier, Caamaño, Aimée, Carmona, Mar, Capron, Alexander, Cardillo, Massimo, Carella, Claudia, Castillo, María Esther, Cervantes, Lilia, Chandrasekar, Akila, Chaouali, Mafaten, Chatzixiros, Efstratios, Ciccocioppo, Rachele, Cillo, Umberto, Cloherty, Jenny, Colenbie, Luc, Coll, Elisabeth, Cooper, Matthew, Correa-Rocha, Rafael, Cortesi, Paolo Angelo, Cozzi, Emanuele, Cuende, Natividad, Cuero, César, Antonio Da Silva, Juan, Daga, Domingo, Danielyan, Samvel, Danovitch, Gabriel, de Andrade, Joel, de Angelis, Vincenzo, Dedinska, Ivana, del Río, Francisco J., Delmonico, Francis L., Di Ciaccio, Paola, Doerr, Petra, Domínguez-Gil, Beatriz, Emery, Marie-Pierre, Espinel, Mauricio, Fadhil, Riadh, Foeken, Lydia, Forsberg, Anna, Forsythe, John L. R., Friend, Peter, Gadžijev, Andrej, Gallego, Daniel, Gardiner, Dale, Gatt, Sandra, Gjerek, Jernej, Gondolesi, Gabriel, Haraldsson, Börje, Hasal, Antonín, Hennerbichler, Simone, Hernández-Maraver, Dolores, Herson, Marisa, Hickey, Laura, Humar, Simona, Ilbawi, Andre, Immer, Franz, Izeta, Ander, Hawthorne, Wayne J., Jha, Vivekanand, Joyce, Ruth, Jusinskis, Janis, Kaminski, Artur, Kazancıoğlu, Rümeyza, Kim, Joe, Lentine, Krista L., Fraga, Marta López, Lundin, Kersti, Mahillo, Beatriz, Maier, Philip, Mallet, Laurent, Manas, Derek, Manyalich, Marti, Marco, Jaime, Martin, Dominique E., Martínez-Donate, María Dolores, Martjak, Marge, McGee, Andrew, McPhaden, Marcelle, Menjívar, Ana, Mey, Devi, Mihály, Sándor, Mihelčič, Petra, Miñambres, Eduardo, Mirabet, Sonia, Mojsova Mijovska, Maja, Montrasio, Lorenzo, María Moraleda, Jose, Morales, Fernando, Mueller, Thomas, Muller, Elmi, Musquera, Mireia, Nagral, Sanjay, Nathan, Naomi, Nikolac, Vanja, Niño Murcia, Alejandro, Noel, Luc, O’Sullivan, Siobhan, Oniscu, Gabriel C., Opdam, Helen, Orlando, Giuseppe, Ortega, Noelia, Padilla, Benita, Papatheodoridis, George, Pérez Bech, Eva, Pérez Blanco, Alicia, Pérez Martínez, Antonio, Perojo, Dolores, Pires Silva, Ana, Plattner, Verena, Porte, Robert, Potashnik, Anna, Potena, Luciano, Gilberto Prasca, Tomás, Premužić, Marina, Procaccio, Francesco, Rahmel, Axel, Randazzo, Enrico, Raptis, Dimitri A, Rela, Mohamed, Resanović, Vladimir, Rizzolo, Katherine, Adina Rugescu, Iona, Ruiz-Pérez, Blanca, Sainte-Marie, Isabelle, Angelica Salinas, Maria, Sánchez Ibáñez, Jacinto, Serrano, Roselyn, Shaheen, Faissal A., Shemie, Sam, Snyder, Jon, Marie Sørensen, Ragnhild, Spiro, Michael, Stock, Peter, Subotić-Popović, Andreja, Gracious, Noble, Sureda, Ana, Tassot, Johanna, ten Ham, Renske, Thomson, David, Timbalari, Tatiana, Torres, Martín, Tort, Jaume, Trias, Esteve, Trojan, Diletta, Tsimaratos, Mitchel, Tullius, Stefan G., Van Assche, Kristof, Van der Spiegel, Stefaan, Vatachki, Guenadiy, Velasco, Belén, Villatoro, Matías, Walsh, John, Wang, Haibo, and Waterman, Amy

Published
2025
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2. Promoting Equitable and Affordable Patient Access to Safe and Effective Innovations in Donation and Transplantation of Substances of Human Origin and Derived Therapies

Author

Cuende, Natividad, Tullius, Stefan G., Izeta, Ander, Plattner, Verena, Börgel, Martin, Ciccocioppo, Rachele, Correa-Rocha, Rafael, Koh, Mickey B. C., De Angelis, Vincenzo, Gondolesi, Gabriel E., ten Ham, Renske, Porte, Robert J., Hernández-Maraver, Dolores, Hawthorne, Wayne J., Sureda, Anna, Orlando, Giuseppe, Haraldsson, Börje, Ascher, Nancy L., Dominguez-Gil, Beatriz, and Oniscu, Gabriel C.

Published
2025
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3. Research opportunities and ethical considerations for heart and lung xenotransplantation research: A report from the National Heart, Lung, and Blood Institute workshop

Author

Khush, Kiran K., Bernat, James L., Pierson, Richard N., III, Silverman, Henry J., Parent, Brendan, Glazier, Alexandra K., Adams, Andrew B., Fishman, Jay A., Gusmano, Michael, Hawthorne, Wayne J., Homan, Mary E., Hurst, Daniel J., Latham, Stephen, Park, Chung-Gyu, Maschke, Karen J., Mohiuddin, Muhammad M., Montgomery, Robert A., Odim, Jonah, Pentz, Rebecca D., Reichart, Bruno, Savulescu, Julian, Wolpe, Paul Root, Wong, Renee P., and Fenton, Kathleen N.

Published
2024
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6. A Pro-Endocrine Pancreatic Islet Transcriptional Program Established During Development Is Retained in Human Gallbladder Epithelial Cells

Author

Joglekar, Mugdha V., Sahu, Subhshri, Wong, Wilson K.M., Satoor, Sarang N., Dong, Charlotte X., Farr, Ryan J., Williams, Michael D., Pandya, Prapti, Jhala, Gaurang, Yang, Sundy N.Y., Chew, Yi Vee, Hetherington, Nicola, Thiruchevlam, Dhan, Mitnala, Sasikala, Rao, Guduru V., Reddy, Duvvuru Nageshwar, Loudovaris, Thomas, Hawthorne, Wayne J., Elefanty, Andrew G., Joglekar, Vinay M., Stanley, Edouard G., Martin, David, Thomas, Helen E., Tosh, David, Dalgaard, Louise T., and Hardikar, Anandwardhan A.

Published
2022
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7. Machine learning workflows identify a microRNA signature of insulin transcription in human tissues

Author

Wong, Wilson K.M., Joglekar, Mugdha V., Saini, Vijit, Jiang, Guozhi, Dong, Charlotte X., Chaitarvornkit, Alissa, Maciag, Grzegorz J., Gerace, Dario, Farr, Ryan J., Satoor, Sarang N., Sahu, Subhshri, Sharangdhar, Tejaswini, Ahmed, Asma S., Chew, Yi Vee, Liuwantara, David, Heng, Benjamin, Lim, Chai K., Hunter, Julie, Januszewski, Andrzej S., Sørensen, Anja E., Akil, Ammira S.A., Gamble, Jennifer R., Loudovaris, Thomas, Kay, Thomas W., Thomas, Helen E., O'Connell, Philip J., Guillemin, Gilles J., Martin, David, Simpson, Ann M., Hawthorne, Wayne J., Dalgaard, Louise T., Ma, Ronald C.W., and Hardikar, Anandwardhan A.

Published
2021
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11. Liraglutide for the Treatment of Severe Hypoglycemia Following Total Pancreatectomy and Islet Autotransplantation.

Author

Chan, Christopher, Hawthorne, Wayne, Pleass, Henry, and Holmes-Walker, Deborah Jane

Subjects
*CONTINUOUS glucose monitoring, *INSULIN shock, *BARIATRIC surgery, *CHRONIC pancreatitis, *ISLANDS of Langerhans
Abstract

Total pancreatectomy and islet autotransplantation (TPIAT) is an effective treatment for chronic and recurrent acute pancreatitis, and it provides a significant potential additional benefit of insulin independence. Spontaneous hypoglycemia in the absence of insulin therapy following TPIAT is a recognized complication, which has been attributed to lack of protective glucagon responses to hypoglycemia, following intrahepatic islet autotransplantation. We describe the use of liraglutide to treat spontaneous hypoglycemia following TPIAT. Continuous glucose monitoring was used to identify timing of hypoglycemia in relation to meals and monitor treatment effect. Liraglutide has been used for management of hypoglycemia following bariatric surgery, but, to our knowledge, this is the first application of its effective use to treat spontaneous severe hypoglycemia following TPIAT. [ABSTRACT FROM AUTHOR]

Published
2024
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22. Exosomes and machine perfusion as a therapy to improve organ transplantation.

Author

Hawthorne, Wayne J., Amaratunga, Rajith, and Hameed, Ahmer

Subjects
*EXTRACELLULAR vesicles, *PRESERVATION of organs, tissues, etc., *MESENCHYMAL stem cells, *CELL preservation, *TRANSPLANTATION of organs, tissues, etc., *CELL communication
Abstract

The article discusses the use of exosomes and machine perfusion as a therapy to improve organ transplantation outcomes. Exosomes, small extracellular vesicles, play a unique role in cellular communication and can be used to reduce ischemia/reperfusion injury in transplanted organs. Studies have shown that exosomes derived from various cell types, including urine progenitor cells, have anti-inflammatory and regenerative properties that can enhance organ preservation and resuscitation methods. While exosome-based therapies show promise in improving transplant outcomes, further research is needed to standardize isolation methods and identify specific bioactive molecules for targeted modifications. [Extracted from the article]

Published
2024
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23. Clonidine inhibits anti‐non‐Gal IgM xenoantibody elicited in multiple pig‐to‐primate models

Author

Stewart, John M, Tarantal, Alice F, Hawthorne, Wayne J, Salvaris, Evelyn J, O'Connell, Philip J, Nottle, Mark B, d'Apice, Anthony JF, Cowan, Peter J, and Kearns-Jonker, Mary

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Biotechnology, Transplantation, Prevention, Vaccine Related, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Animals, Antibodies, Heterophile, Clonidine, Gene Knockout Techniques, Heterografts, Immunoglobulin M, Macaca mulatta, Models, Animal, Papio, Sus scrofa, Swine, Transplantation, Heterologous, baboon, clonidine, endothelial cell, islet, kidney, pig, rhesus monkey, small molecule, xenotransplantation, Surgery, Clinical sciences
Abstract

BackgroundSurvival of vascularized xenografts is dependent on pre-emptive inhibition of the xenoantibody response against galactosyltransferase knockout (GTKO) porcine organs. Our analysis in multiple GTKO pig-to-primate models of xenotransplantation has demonstrated that the anti-non-gal-α-1,3-gal (anti-non-Gal) xenoantibody response displays limited structural diversity. This allowed our group to identify an experimental compound which selectively inhibited induced anti-non-Gal IgM xenoantibodies. However, because this compound had an unknown safety profile, we extended this line of research to include screening small molecules with known safety profiles allowing rapid advancement to large animal models.MethodsThe NIH clinical collections of small molecules were screened by ELISA for their ability to inhibit xenoantibody binding to GTKO pig endothelial cells. Serum collected from non-immunosuppressed rhesus monkeys at day 14 post-injection with GTKO pig endothelial cells was utilized as a source of elicited xenoantibody for initial screening. Virtual small molecule screening based on xenoantibody structure was used to assess the likelihood that the identified small molecules bound xenoantibody directly. As a proxy for selectivity, ELISAs against tetanus toxoid and the natural antigens laminin, thyroglobulin, and single-stranded DNA (ssDNA) were utilized to assess the ability of the identified reagents to inhibit additional antibody responses. The identified inhibitory small molecules were further tested for their ability to inhibit xenoantibody elicited in multiple settings, including rhesus monkeys pre-treated with an anti-non-Gal selective anti-idiotypic antibody, non-immunosuppressed rhesus monkeys immunized with wild-type fetal pig isletlike cell clusters, and non-immunosuppressed baboons transplanted with GTKO multiple transgenic pig kidneys.ResultsFour clinically relevant small molecules inhibited anti-non-Gal IgM binding to GTKO pig endothelial cells in vitro. Three of these drugs displayed a limited region of structural similarity suggesting they may inhibit xenoantibody by a similar mechanism. One of these, the anti-hypertensive agent clonidine, displayed only minimal inhibition of antibodies elicited by vaccination against tetanus toxoid or pre-existing natural antibodies against laminin, thyroglobulin, or ssDNA. Furthermore, clonidine inhibited elicited anti-non-Gal IgM from all animals that demonstrated a xenoantibody response in each experimental setting.ConclusionsClinically relevant small molecule drugs with known safety profiles can inhibit xenoantibody elicited against non-Gal antigens in diverse experimental xenotransplantation settings. These molecules are ready to be tested in large animal models. However, it will first be necessary to optimize the timing and dosing required to inhibit xenoantibodies in vivo.

Published
2015

25. Rhesus monkeys and baboons develop clotting factor VIII inhibitors in response to porcine endothelial cells or islets

Author

Stewart, John M, Tarantal, Alice F, Hawthorne, Wayne J, Salvaris, Evelyn J, O'Connell, Philip J, Nottle, Mark B, d'Apice, Anthony JF, Cowan, Peter J, and Kearns‐Jonker, Mary

Subjects
Biomedical and Clinical Sciences, Immunology, Hematology, Organ Transplantation, Biotechnology, Transplantation, Amino Acid Sequence, Animals, Animals, Genetically Modified, Antibodies, Heterophile, Computer Simulation, Endothelial Cells, Factor VIII, Galactosyltransferases, Gene Knockout Techniques, Humans, Islets of Langerhans Transplantation, Macaca mulatta, Models, Molecular, Molecular Sequence Data, Mutagenesis, Site-Directed, Papio, Protein Interaction Domains and Motifs, Recombinant Proteins, Sequence Homology, Amino Acid, Sus scrofa, Transplantation, Heterologous, clotting factor VIII, clotting factor VIII inhibitor, non-human primate, porcine, xenoantibody, Clinical Sciences, Surgery, Clinical sciences
Abstract

BackgroundXenotransplantation of porcine organs holds promise of solving the human organ donor shortage. The use of α-1,3-galactosyltransferase knockout (GTKO) pig donors mitigates hyperacute rejection, while delayed rejection is currently precipitated by potent immune and hemostatic complications. Previous analysis by our laboratory suggests that clotting factor VIII (FVIII) inhibitors might be elicited by the structurally restricted xenoantibody response which occurs after transplantation of either pig GTKO/hCD55/hCD59/hHT transgenic neonatal islet cell clusters or GTKO endothelial cells.MethodsA recombinant xenoantibody was generated using sequences from baboons demonstrating an active xenoantibody response at day 28 after GTKO/hCD55/hCD59/hHT transgenic pig neonatal islet cell cluster transplantation. Rhesus monkeys were immunized with GTKO pig endothelial cells to stimulate an anti-non-Gal xenoantibody response. Serum was collected at days 0 and 7 after immunization. A two-stage chromogenic assay was used to measure FVIII cofactor activity and identify antibodies which inhibit FVIII function. Molecular modeling and molecular dynamics simulations were used to predict antibody structure and the residues which contribute to antibody-FVIII interactions. Competition ELISA was used to verify predictions at the domain structural level.ResultsAntibodies that inhibit recombinant human FVIII function are elicited after non-human primates are transplanted with either GTKO pig neonatal islet cell clusters or endothelial cells. There is an apparent increase in inhibitor titer by 15 Bethesda units (Bu) after transplant, where an increase greater than 5 Bu can indicate pathology in humans. Furthermore, competition ELISA verifies the computer modeled prediction that the recombinant xenoantibody, H66K12, binds the C1 domain of FVIII.ConclusionsThe development of FVIII inhibitors is a novel illustration of the potential impact the humoral immune response can have on coagulative dysfunction in xenotransplantation. However, the contribution of these antibodies to rejection pathology requires further evaluation because "normal" coagulation parameters after successful xenotransplantation are not fully understood.

Published
2014

37. Brief Normothermic Machine Perfusion Rejuvenates Discarded Human Kidneys

Author

Hameed, Ahmer M., Lu, David B., Patrick, Ellis, Xu, Bo, Hu, Min, Chew, Yi Vee, Keung, Karen, P’ng, Chow H., Gaspi, Renan, Zhang, Chris, Robertson, Paul, Alexander, Stephen, Thomas, Gordon, Laurence, Jerome, De Roo, Ronald, Wong, Germaine, Miraziz, Ray, O’Grady, Greg, Yuen, Lawrence, Hawthorne, Wayne J., Rogers, Natasha M., and Pleass, Henry C.

Published
2019
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38. Ethical and legislative advances in xenotransplantation for clinical translation: focusing on cardiac, kidney and islet cell xenotransplantation.

Author

Hawthorne, Wayne J.

Subjects
XENOTRANSPLANTATION, ISLANDS of Langerhans, PATIENT advocacy, XENOGRAFTS, KIDNEYS
Abstract

In this state-of-the-art review we detail the journey of xenotransplantation from its infancy, detailing one of the first published cases and the subsequent journey the field took in its inception and development. With a focus on the science, technological advances, precautions required along with the potential limitations in application, the ethics, guidance's, and legislative advances that are required to reach the safe and efficacious clinical application of xenotransplantation. Along with a view over the past several decades with the overall significant advancements in pre-clinical study outcomes particularly in islet, kidney, and heart xenotransplantation, to ultimately reach the pinnacle of successful clinical heart and kidney xenotransplants. It outlines the importance for the appropriate guidance's required to have been developed by experts, scientists, clinicians, and other players who helped develop the field over the past decades. It also touches upon patient advocacy along with perspectives and expectations of patients, along with public opinion and media influence on the understanding and perception of xenotransplantation. It discusses the legislative environment in different jurisdictions which are reviewed in line with current clinical practices. All of which are ultimately based upon the guidance's developed from a strong long-term collaboration between the International Xenotransplantation Association, the World Health Organisation and The Transplantation Society; each having constantly undertaken consultation and outreach to help develop best practice for clinical xenotransplantation application. These clearly helped forge the legislative frameworks required along with harmonization and standardization of regulations which are detailed here. Also, in relation to the significant advances in the context of initial xeno-kidney trials and the even greater potential for clinical xeno-islet trials to commence we discuss the significant advantages of xenotransplantation and the ultimate benefit to our patients. [ABSTRACT FROM AUTHOR]

Published
2024
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39. Characterisation of transgenic pigs expressing a human T cell‐depleting anti‐CD2 monoclonal antibody.

Author

Salvaris, Evelyn J., Fisicaro, Nella, McIlfatrick, Stephen, Thomas, Adwin, Fuller, Erin, Lew, Andrew M., Nottle, Mark B., Hawthorne, Wayne J., and Cowan, Peter J.

Subjects
SOMATIC cell nuclear transfer, MONOCLONAL antibodies, SWINE, WHOLE genome sequencing, TYPE 1 diabetes
Abstract

Background: Pig islet xenotransplantation is a potential treatment for type 1 diabetes. We have shown that maintenance immunosuppression is required to protect genetically modified (GM) porcine islet xenografts from T cell‐mediated rejection in baboons. Local expression of a depleting anti‐CD2 monoclonal antibody (mAb) by the xenograft may provide an alternative solution. We have previously reported the generation of GGTA1 knock‐in transgenic pigs expressing the chimeric anti‐CD2 mAb diliximab under an MHC class I promoter (MHCIP). In this study, we generated GGTA1 knock‐in pigs in which MHCIP was replaced by the β‐cell‐specific porcine insulin promoter (PIP), and compared the pattern of diliximab expression in the two lines. Methods: A PIP‐diliximab knock‐in construct was prepared and validated by transfection of NIT‐1 mouse insulinoma cells. The construct was knocked into GGTA1 in wild type (WT) porcine fetal fibroblasts using CRISPR, and knock‐in cells were used to generate pigs by somatic cell nuclear transfer (SCNT). Expression of the transgene in MHCIP‐diliximab and PIP‐diliximab knock‐in pigs was characterised at the mRNA and protein levels using RT‐qPCR, flow cytometry, ELISA and immunohistochemistry. Islets from MHCIP‐diliximab and control GGTA1 KO neonatal pigs were transplanted under the kidney capsule of streptozotocin‐diabetic SCID mice. Results: NIT‐1 cells stably transfected with the PIP‐diliximab knock‐in construct secreted diliximab into the culture supernatant, confirming correct expression and processing of the mAb in β cells. PIP‐diliximab knock‐in pigs showed a precise integration of the transgene within GGTA1. Diliximab mRNA was detected in all tissues tested (spleen, kidney, heart, liver, lung, pancreas) in MHCIP‐diliximab pigs, but was not detectable in PIP‐diliximab pigs. Likewise, diliximab was present in the serum of MHCIP‐diliximab pigs, at a mean concentration of 1.8 μg/mL, but was not detected in PIP‐diliximab pig serum. An immunohistochemical survey revealed staining for diliximab in all organs of MHCIP‐diliximab pigs but not of PIP‐diliximab pigs. Whole genome sequencing (WGS) of a PIP‐diliximab pig identified a missense mutation in the coding region for the dixilimab light chain. This mutation was also found to be present in the fibroblast knock‐in clone used to generate the PIP‐diliximab pigs. Islet xenografts from neonatal MHCIP‐diliximab pigs restored normoglycemia in diabetic immunodeficient mice, indicating no overt effect of the transgene on islet function, and demonstrated expression of diliximab in situ. Conclusion: Diliximab was widely expressed in MHCIP‐diliximab pigs, including in islets, consistent with the endogenous expression pattern of MHC class I. Further investigation is required to determine whether the level of expression in islets from the MHCIP‐diliximab pigs is sufficient to prevent T cell‐mediated islet xenograft rejection. The unexpected absence of diliximab expression in the islets of PIP‐diliximab pigs was probably due to a mutation in the transgene arising during the generation of the knock‐in cells used for SCNT. [ABSTRACT FROM AUTHOR]

Published
2024
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