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Development of a rat liver machine perfusion system for normothermic and subnormothermic conditions
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Tissue Engineering Part A accepted our paper on the "Development of a rat liver machine perfusion system for normothermic and subnormothermic conditions" (Tissue Eng Part A. 2019 Jul 31. doi: 10.1089/ten.TEA.2019.0152. [Epub ahead of print[) !
Ex vivo liver machine perfusion is a promising alternative for preservation of liver grafts from extended criteria donors. Small animal models can be used to evaluate different perfusion conditions. We here describe the development of a miniaturized ex vivo machine perfusion system for rat liver grafts, evaluating cell-free and erythrocyte-based perfusion solutions, subnormothermic and normothermic temperatures and dialysis. A perfusion chamber was designed after a suitable liver position was identified. Normothermic ex vivo liver perfusion (NEVLP) required supplementation of erythrocytes to reduce cell damage. Perfusion with erythrocytes led to rising potassium levels after 12 hours (NEVLP, 16.2mmol/l, interquartile range (IQR) 5.7 and subnormothermic ex vivo liver perfusion (SNEVLP), 12.8 mmol/l, IQR 3.5), which were normalized by dialysis using a laboratory dialysis membrane (NEVLP, 6.2 mmol/l, IQR 0.5 and SNEVLP, 5.3 mmol/l, IQR 0.1; p=0.004). Livers treated with NEVLP conditions showed higher bile production (18.52mg/h/g, IQR 8.2) compared to livers perfused under SNEVLP conditions (0.4 mg/h/g, IQR 1.2, p=0.01). Reducing the perfusion volume from 100ml to 50ml allowed for higher erythrocytes concentrations, leading to significantly lower transaminases (15.75 U/l/ml, IQR 2.29 vs. 5.97 U/l/ml, IQR 18.07, p=0.002). In conclusion, a well-designed perfusion system, appropriate oxygen carriers, dialysis, and miniaturization of the perfusion volume are critical features for successful miniaturized ex vivo liver machine perfusion.

Authors are M. Nösser, J.M.G.V. Gassner, S. Moosburner, D. Wyrwal, F. Claussen, K.H. Hillebrandt, R. Horner, P. Tang, A. Reutzel-Selke, D. Polenz, R. Arsenic, J. Pratschke, I.M. Sauer, and N. Raschzok.
Priv.-Doz. Dr. Felix Krenzien & Priv.-Doz. Dr. Christian Benzing
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Today Dr. Felix Krenzien and Dr. Christian Benzing received they post-doctoral lecturing qualification (Habilitation) at Charité – Universitätsmedizin Berlin.
The title of Felix Krenzien's Habilitationsschrift is "Der differenzierte Einfluss der Seneszenz auf die Organtransplantation und Leberteilresektion", Christian Benzing focussed on the "Untersuchung der gesundheitsbezogenen Lebensqualität und der psychischen Gesundheit nach Lebertransplantation".

Congratulations !
Impact of Percoll purification on isolation of primary human hepatocytes
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Scientific Reports published our paper "Impact of Percoll purification on isolation of primary human hepatocytes" (Sci Rep. 2019 Apr 25;9(1):6542). Authors are R. Horner, J.G.M.V. Gassner, M. Kluge, P. Tang, S. Lippert, K.H. Hillebrandt, S. Moosburner, A. Reutzel-Selke, J. Pratschke, I.M. Sauer, and N. Raschzok.

Research and therapeutic applications create a high demand for primary human hepatocytes. The limiting factor for their utilization is the availability of metabolically active hepatocytes in large quantities. Centrifugation through Percoll, which is commonly performed during hepatocyte isolation, has so far not been systematically evaluated in the scientific literature. 27 hepatocyte isolations were performed using a two-step perfusion technique on tissue obtained from partial liver resections. Cells were seeded with or without having undergone the centrifugation step through 25% Percoll. Cell yield, function, purity, viability and rate of bacterial contamination were assessed over a period of 6 days. Viable yield without Percoll purification was 42.4 × 106 (SEM ± 4.6 × 106) cells/g tissue. An average of 59% of cells were recovered after Percoll treatment. There were neither significant differences in the functional performance of cells, nor regarding presence of non-parenchymal liver cells. In five cases with initial viability of <80%, viability was significantly increased by Percoll purification (71.6 to 87.7%, p = 0.03). Considering our data and the massive cell loss due to Percoll purification, we suggest that this step can be omitted if the initial viability is high, whereas low viabilities can be improved by Percoll centrifugation.
Critical Care for Potential Liver Transplant Candidates
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The book Critical Care for Potential Liver Transplant Candidates
(D. Bezinover and F. Saner [Eds.]) focuses on patients with end-stage-liver disease (ESLD) who could possibly qualify for liver transplant. This patient cohort raises many problems: who should be treated and also, when is it too late for transplant? The authors are all dedicated experts in the field of ESLD/liver transplantation, but from different disciplines with different views of the problem.
In the past 15 years many things have changed in the treatment for these patients: cardiac assessment, treatment of porto-pulmonary hypertension, hemodynamics, coagulation assessment and management, diagnosis of kidney failure, and the timing of dialysis. These issues are comprehensively discussed in this book, in order to provide physicians starting in the field of transplantation an overview of different areas of concern.
This book is aimed at specialists and trainees in critical care, hepatology, anesthesia, surgery, and nephrology.

N. Raschzok, K.H. Hillebrandt and I.M. Sauer contributed with the chapter "Liver Assist Systems for Bridging to Transplantation: Devices and Concepts".

More information via this link.
Read More
Critical Care for Potential Liver Transplant Candidates
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The book Critical Care for Potential Liver Transplant Candidates
(D. Bezinover and F. Saner [Eds.]) focuses on patients with end-stage-liver disease (ESLD) who could possibly qualify for liver transplant. This patient cohort raises many problems: who should be treated and also, when is it too late for transplant? The authors are all dedicated experts in the field of ESLD/liver transplantation, but from different disciplines with different views of the problem.
In the past 15 years many things have changed in the treatment for these patients: cardiac assessment, treatment of porto-pulmonary hypertension, hemodynamics, coagulation assessment and management, diagnosis of kidney failure, and the timing of dialysis. These issues are comprehensively discussed in this book, in order to provide physicians starting in the field of transplantation an overview of different areas of concern.
This book is aimed at specialists and trainees in critical care, hepatology, anesthesia, surgery, and nephrology.

N. Raschzok, K.H. Hillebrandt and I.M. Sauer contributed with the chapter "Liver Assist Systems for Bridging to Transplantation: Devices and Concepts".

More information via this link.
Read More
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Our manuscript "Depletion of donor dendritic cells ameliorates immunogenicity of both skin and hind limb transplants" has been accepted for publication in Frontiers in Immunology, section Alloimmunity and Transplantation. Authors are Muhammad Imtiaz Ashraf, Joerg Mengwasser, Anja Reutzel-Selke, Dietrich Polenz, Kirsten Führer, Steffen Lippert, Peter Tang, Edward Michaelis, Rusan Catar, Johann Pratschke, Christian Witzel, Igor M. Sauer, Stefan G. Tullius, and Barbara Kern.

Acute cellular rejection remains a significant obstacle affecting successful outcomes of organ transplantation including vascularized composite tissue allografts (VCA). Donor antigen presenting cells (APC), particularly dendritic cells (DC), orchestrate early alloimmune responses by activating recipient effector T cells. Employing a targeted approach, we investigated the impact of donor-derived conventional DC (cDC) and APC on the immunogenicity of skin and skin-containing VCA grafts, using mouse models of skin and hind limb transplantation.
By post-transplantation day 6, skin grafts demonstrated severe rejections, characterized by predominance of recipient CD4 T cells. In contrast, hind limb grafts showed moderate rejection, primarily infiltrated by CD8 T cells. While donor depletion of cDC and APC reduced frequencies, maturation, and activation of DC in all analysed tissues of skin transplant recipients, reduction in DC activities was only observed in the spleen of hind limb recipients. Donor cDC and APC depletion did not impact all lymphocyte compartments but significantly affected CD8 T cells and activated CD4 T in lymph nodes of skin recipients. Moreover, both donor APC and cDC depletion attenuated the Th17 immune response, evident by significantly reduced Th17 (CD4+IL-17+) cells in the spleen of skin recipients and reduced levels of IL-17E and lymphotoxin-α in the serum samples of both skin and hind limb recipients. In conclusion, our findings underscore the highly immunogenic nature of skin component in VCA. The depletion of donor APC and cDC mitigates the immunogenicity of skin grafts while exerting minimal impact on VCA.

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