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Early markers of reperfusion injury after liver transplantation: association with primary dysfunction

Hepatobiliary & Pancreatic Diseases International 2015年第3期14卷 246-252页

作者： helge bruns Jan Heil Daniel Schultze Mohammed Al Saeedi Peter Schemmer Department of General and Transplant Surgery University Hospital Heidelberg

BACKGROUND： In patients with end-stage fiver disease, fiver transplantation is the only available curative treatment. Al- though the outcome and quality of life in the patients have improved over the past decades, primary dys- or nonfimction （PDF/PNF） can occur. Early detection of PDF and PNF is crucial and could lead to individual therapies. This study was designed to identify early markers of reperfusion injury and PDF in liver biopsies taken during the first hour after reperfusion.

关键词： primary dysfunction liver transplantation predictive markers reperfusion injury microarray

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Hepatocytic differentiation of mesenchymal stem cells in cocultures with fetal liver cells

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World Journal of Gastroenterology 2006年第15期12卷 2394-2397页

作者： Claudia Lange helge bruns Dietrich Kluth Axel R Zander Henning C Fiegel Center of Bone Marrow Transplantation University Hospital Hamburg-Eppendorf Martinistrasse 52D-20246 HamburgGermany Department of Pediatric Surgery University Hospital Hamburg-Eppendorf Martinistrasse 52D-20246 HamburgGermany Department of Pediatric Surgery University Hospital Hamburg-Eppendorf Martinistrasse 52D-20246 Hamburg Germany

AIM： To investigate the hepatocytic differentiation of mesenchymal stem cells （MSCs） in co-cultures with fetal liver cells （FLC） and the possibility to expand differentiated hepatocytic cells. METHODS： MSCs were marked with green fluorescent protein （GFP） by retroviral gene transduction. Clonal marked MSCs were either cultured under liver stimulating conditions using fibronectin-coated culture dishes and medium supplemented with stem cell factor （SCF）, hepatocyte growth factor （HGF）, epidermal growth factor （EGF）, and fibroblast growth factor 4 （FGF-4） alone, or in presence of freshly isolated FLC. Cells in co-cultures were harvested, and GFP＋ or GFP- cells were separated using fluorescence activated cell sorting. Reverse transcription-polymerase chain reaction （RT-PCR） for the liver specific markers cytokeratin-18 （CK-18）, albumin, and alpha-fetoprotein （AFP） was performed in different cell populations. RESULTS- Under the specified culture conditions, rat MSCs co-cultured with FLC expressed albumin, CK-18, and AFP-RNA over two weeks. At wk 3, MSCs lost hepatocytic gene expression, probably due to overgrowth of the cocultured FLC. FLC also showed a stable liver specific gene expression in the co-cultures and a very high growth potential. CONCLUSION： The rat MSCs from bone marrow can differentiate hepatocytic cells in the presence of FLC in vitro and the presence of MSCs in co-cultures also prorides a beneficial environment for expansion and differentiation of FLC.

关键词： Hepatic stem cells Mesenchymal stem cells Fetal liver cells Co-culture

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Quality of life after curative liver resection: A single center analysis

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World Journal of Gastroenterology 2010年第19期16卷 2388-2395页

作者： helge bruns Kirsten Krtschmer Ulf Hinz Anette Brechtel Monika Keller Markus W Büchler Peter Schemmer Department of General Surgery Ruprecht-Karls-University 69120 Heidelberg Germany Psychosomatic Medicine Section Psychooncology Ruprecht-Karls-University 69120 Heidelberg Germany

AIM: To evaluate quality of life (QoL) after curative liver resection and identify variables associated with decreased QoL. METHODS: From October 2001 to July 2004, 323 patients underwent liver resection. At 3-36 mo after discharge, 188 patients were disease free. QoL was assessed using the Short Form (SF)-12 Health Survey with mental and physical component scales (SF-12 MCS and PCS), supplemented with generic questions concerning pain and liver-specific items. RESULTS: Sixty-eight percent (128/188) returned the questionnaire, which was completed in 75% (96/128) of cases. Median SF-12 PCS and MCS were 46.7 (inter- quartile range: 34.2-53.9) and 54.1 (42.8-58.2). Fifty percent were pain free with a median symptom score of 1.75 (1.38-2.13). PCS was higher after major hepatec-tomy [57% (55/96)] compared to minor resection (P = 0.0049), which represented an improved QoL. QoL was not affected by sex but by age compared to the general German population. MCS was higher after liver surgery for metastatic disease [55.9 (47.5-58.8)] compared to primary carcinoma [49.6 (36.5-55.1)] and benign disease [49.2 (37.7-56.3)] (P = 0.0317). There was no correlation between length of postoperative period and QoL. Pain, def iciencies in everyday life and a high symptom score significantly decreased MCS and PCS. CONCLUSION: Most patients were only marginally affected even after major liver resection; however, minor complications were associated with decreased SF-12 MCS and PCS and need careful attention.

关键词： Quality of life Liver resection

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Liver-specific gene expression in mesenchymal stem cells is induced by liver cells

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World Journal of Gastroenterology 2005年第29期11卷 4497-4504页

作者： Claudia Lange Philipp Bassler Michael V. Lioznov helge bruns Dietrich Kluth Axel R. Zander Henning C. Fiegel Center of Bone Marrow Transplantation University Hospital Hamburg-Eppendorf Martinistrasse 52 D-20246 Hamburg Germany Department of Pediatric Surgery University Hospital Hamburg-Eppendorf Martinistrasse 52 D-20246 Hamburg Germany

AIM： The origin of putative liver cells from distinct bone marrow stem cells, e.g. hematopoietic stem cells or multipotent adult progenitor cells was found in recent in vitro studies. Cell culture experiments revealed a key role of growth factors for the induction of liver-specific genes in stern cell cultures. We investigated the potential of rat mesenchymal stem cells （MSC） from bone marrow to differentiate into hepatocytic cells in vitro. Furthermore, we assessed the influence of cocultured liver cells on induction of liver-specific gene expression. METHODS： Mesenchymal stem cells were marked with green fluorescent protein （GFP） by retroviral gene transduction. Clonal marked MSC were either cultured under liver stimulating conditions using fibronectin-coated culture dishes and medium supplemented with SCF, HGF, EGF, and FGF-4 alone, or in presence of freshly isolated rat liver cells. Cells in cocultures were harvested and GFP＋ or GFP- cells were separated using fluorescence activated cell sorting. RT-PCR analysis for the stem cell marker Thyl and the hepatocytic markers CK-18, albumin, CK-19, and AFP was performed in the different cell populations. RESULTS： Under the specified culture conditions, rat MSC cocultured with liver cells expressed albumin-, CK-18, CK-19, and AFP-RNA over 3 weeks, whereas MSC cultured alone did not show liver specific gene expression, CONCLUSION： The results indicate that （1） rat MSC from bone marrow can differentiate towards hepatocytic lineage in vitro, and （2） that the microenvironment plays a decisive role for the induction of hepatic differentiation of rMSC.

关键词： Mesenchymal stem cells Liver-specific differentiation Coculture

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大鼠肾移植1000例经验总结

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中国组织工程研究与临床康复 2011年第5期15卷 891-893页

作者：李占清关晓海王世军陈晶伊雪邬鹏宇肖志 Nickkholgh Arash bruns helge Hoffmann Katrin Schemmer Peter 华北煤炭医学院附属医院河北省唐山市063000 海德堡大学移植中心德国癌症研究中心

目的:对大鼠肾移植进行经验总结以指导实验与临床研究。方法:作者在2004-01/2009-07海德堡大学移植中心期间,采用大鼠肾动、静脉与腹主动脉、腔静脉行端侧吻合。对于急性肾移植模型,输尿管直接植入膀胱内;对于慢性肾移植模型,输尿管采... 详细信息

目的:对大鼠肾移植进行经验总结以指导实验与临床研究。方法:作者在2004-01/2009-07海德堡大学移植中心期间,采用大鼠肾动、静脉与腹主动脉、腔静脉行端侧吻合。对于急性肾移植模型,输尿管直接植入膀胱内;对于慢性肾移植模型,输尿管采用端端吻合法。术中直接切除对侧肾脏,完成大鼠肾移植1000例,并对其进行总结。结果:只要供体肾脏冲洗良好,吻合时暖缺血时间小于30min,手术时间60min左右,吻合技术娴熟,移植成功率达98%以上。结论:该实验模型安全、方便、可行。肾移植成功的关键是手术技术。

关键词：大鼠肾移植动物模型成功率器官移植

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