GENETIC MODIFICATIONS OF THE PORCINE GENOME REGULATE INFLAMMATORY AND COAGULATION RESPONSES DURING EX-VIVO PORCINE LIVER PERFUSION WITH HUMAN BLOOD

Introduction Human donor organ shortages have led surgeons and scientists to explore the use of animals as alternative organ sources. Acute thrombovascular rejection (AVR) is the main hurdle in xenotransplantation. Disparities in nucleotide metabolism in the vessels of different species may contribute significantly to the microvascular component of AVR. Methods We evaluated the extent of nucleotide metabolism mismatch in selected organs and endothelial cells of different mammals with particular focus on the changes in activity of ecto-5’-nucleotidase (E5’N) elicited by exposure of porcine hearts or endothelial cells to human blood (ex vivo) or human plasma (in vitro). Results E5’N activity in the rat heart was significantly higher than in other species. We noted a significant difference (p<0.001) in E5’N activity between human and pig endothelial cell lines. Initial pig aortic endothelial E5’N activity decreased in vitro after a three-hour exposure to human and porcine plasma while remaining constant in controls. Ex vivo perfusion with fresh human blood for four hours resulted in a significant decrease of E5’N activity in both wild type and transgenic pig hearts overexpressing human decay accelerating factor (p<0.001). Conclusions This study provides evidence that mismatches in basal mammalian metabolic pathways and humoral immunity interact in a xenogeneic environment. Understanding the role of nucleotide metabolism and signalling in xenotransplantation may identify new targets for genetic modifications and may lead to the development of new therapies extending graft survival.

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Model Assisted Analysis of the Hepatic Arterial Buffer Response During Ex Vivo Porcine Liver Perfusion

IEEE Transactions on Biomedical Engineering ◽

10.1109/tbme.2019.2919413 ◽

2020 ◽

Vol 67 (3) ◽

pp. 667-678 ◽

Cited By ~ 4

Author(s):

Dustin Becker ◽

Max Hefti ◽

Martin J. Schuler ◽

Lucia Bautista Borrego ◽

Catherine Hagedorn ◽

...

Keyword(s):

Ex Vivo ◽

Liver Perfusion ◽

Porcine Liver ◽

Assisted Analysis

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Meta-analysis of the independent and cumulative effects of multiple genetic modifications on pig lung xenograft performance during ex vivo perfusion with human blood

Xenotransplantation ◽

10.1111/xen.12149 ◽

2014 ◽

Vol 22 (2) ◽

pp. 102-111 ◽

Cited By ~ 34

Author(s):

Donald G. Harris ◽

Kevin J. Quinn ◽

Beth M. French ◽

Evan Schwartz ◽

Elizabeth Kang ◽

...

Keyword(s):

Human Blood ◽

Ex Vivo ◽

Meta Analysis ◽

Cumulative Effects ◽

Ex Vivo Perfusion ◽

Genetic Modifications

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Frequency and average gray-level information for thermal ablation status in ultrasound B-Mode sequences

Current Directions in Biomedical Engineering ◽

10.1515/cdbme-2020-0023 ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Jens Ziegle ◽

Alfredo Illanes ◽

Axel Boese ◽

Michael Friebe

Keyword(s):

Thermal Ablation ◽

Ex Vivo ◽

Cell Damage ◽

Potential Temperature ◽

Image Sequences ◽

Target Tissue ◽

Gray Level ◽

Porcine Liver ◽

Time Frequency ◽

Average Gray Level

AbstractDuring thermal ablation in a target tissue the information about temperature is crucial for decision making of successful therapy. An observable temporal and spatial temperature propagation would give a visual feedback of irreversible cell damage of the target tissue. Potential temperature features in ultrasound (US) B-Mode image sequences during radiofrequency (RF) ablation in ex-vivo porcine liver were found and analysed. These features could help to detect the transition between reversible and irreversible damage of the ablated target tissue. Experimental RF ablations of ex-vivo porcine liver were imaged with US B-Mode imaging and image sequences were recorded. Temperature was simultaneously measured within the liver tissue around a bipolar RF needle electrode. In the B-Mode images, regions of interest (ROIs) around the centre of the measurement spots were analysed in post-processing using average gray-level (AVGL) compared against temperature. The pole of maximum energy level in the time-frequency domain of the AVGL changes was investigated in relation to the measured temperatures. Frequency shifts of the pole were observed which could be related to transitions between the states of tissue damage.

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