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The Endothelial Glycocalyx in Pig-to-Baboon Cardiac Xenotransplantation—First Insights

Bender, Martin ; Abicht, Jan Michael ; Reichart, Bruno ; Leuschen, Maria ; Wall, Felicia ; Radan, Julia ; Neumann, Elisabeth ; Mokelke, Maren ; Buttgereit, Ines and Michel, Sebastian , et al. (2024) In Biomedicines 12(6).
Abstract

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 for long-term xenograft acceptance and new insights into innate and adaptive immune responses as well as detailed characterizations of signaling pathways are necessary. In allotransplantation, endothelial cells and their sugar-rich surface—the endothelial glycocalyx—are known to influence organ rejection. In xenotransplantation, however, only in vitro data exist on the role of the endothelial glycocalyx so far. Thus, in the current study, we analyzed the changes of the endothelial glycocalyx... (More)

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 for long-term xenograft acceptance and new insights into innate and adaptive immune responses as well as detailed characterizations of signaling pathways are necessary. In allotransplantation, endothelial cells and their sugar-rich surface—the endothelial glycocalyx—are known to influence organ rejection. In xenotransplantation, however, only in vitro data exist on the role of the endothelial glycocalyx so far. Thus, in the current study, we analyzed the changes of the endothelial glycocalyx components hyaluronan, heparan sulfate and syndecan-1 after pig-to-baboon cardiac xenotransplantations in the perioperative (n = 4) and postoperative (n = 5) periods. These analyses provide first insights into changes of the endothelial glycocalyx after pig-to-baboon cardiac xenotransplantation and show that damage to the endothelial glycocalyx seems to be comparable or even less pronounced than in similar human settings when current strategies of cardiac xenotransplantation are applied. At the same time, data from the experiments where current strategies, like non-ischemic preservation, growth inhibition or porcine cytomegalovirus (a porcine roseolovirus (PCMV/PRV)) elimination could not be applied indicate that damage of the endothelial glycocalyx also plays an important role in cardiac xenotransplantation.

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@article{e3b56fd7-7922-4f73-8084-cf5e7c51d1c6,
  abstract     = {{<p>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 for long-term xenograft acceptance and new insights into innate and adaptive immune responses as well as detailed characterizations of signaling pathways are necessary. In allotransplantation, endothelial cells and their sugar-rich surface—the endothelial glycocalyx—are known to influence organ rejection. In xenotransplantation, however, only in vitro data exist on the role of the endothelial glycocalyx so far. Thus, in the current study, we analyzed the changes of the endothelial glycocalyx components hyaluronan, heparan sulfate and syndecan-1 after pig-to-baboon cardiac xenotransplantations in the perioperative (n = 4) and postoperative (n = 5) periods. These analyses provide first insights into changes of the endothelial glycocalyx after pig-to-baboon cardiac xenotransplantation and show that damage to the endothelial glycocalyx seems to be comparable or even less pronounced than in similar human settings when current strategies of cardiac xenotransplantation are applied. At the same time, data from the experiments where current strategies, like non-ischemic preservation, growth inhibition or porcine cytomegalovirus (a porcine roseolovirus (PCMV/PRV)) elimination could not be applied indicate that damage of the endothelial glycocalyx also plays an important role in cardiac xenotransplantation.</p>}},
  author       = {{Bender, Martin and Abicht, Jan Michael and Reichart, Bruno and Leuschen, Maria and Wall, Felicia and Radan, Julia and Neumann, Elisabeth and Mokelke, Maren and Buttgereit, Ines and Michel, Sebastian and Ellgass, Reinhard and Gieseke, Katja and Steen, Stig and Paskevicius, Audrius and Denner, Joachim and Godehardt, Antonia W. and Tönjes, Ralf R. and Hagl, Christian and Ayares, David and Wolf, Eckhard and Schmoeckel, Michael and Brenner, Paolo and Müller, Martin B. and Längin, Matthias}},
  issn         = {{2227-9059}},
  keywords     = {{endothelial activation; endothelial glycocalyx; heart; organ preservation; orthotopic heart transplantation; xenotransplantation}},
  language     = {{eng}},
  number       = {{6}},
  publisher    = {{MDPI AG}},
  series       = {{Biomedicines}},
  title        = {{The Endothelial Glycocalyx in Pig-to-Baboon Cardiac Xenotransplantation—First Insights}},
  url          = {{http://dx.doi.org/10.3390/biomedicines12061336}},
  doi          = {{10.3390/biomedicines12061336}},
  volume       = {{12}},
  year         = {{2024}},
}