CD133+ adult bone marrow stem cells to promote liver regeneration - the role of platelets for hepatic homing and analyses of released factors for differentiation as well as proliferation subsequent to clinical hepatic resection

CD133成体骨髓干细胞促进肝再生——血小板在肝归巢中的作用以及临床肝切除术后分化和增殖释放因子的分析

• 批准号: 115731935
• 负责人: Professor Dr. Jan Schulte am Esch
• 金额: --
• 依托单位: Klinik für Allgemein-, Viszeral- und Kinderchirurgie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/115731935?language=en
• 关键词: CD133+; adult; bone; marrow; stem

Initial clinical experience with a novel concept to promote liver regeneration in 8 patients, scheduled for extended right liver resection, demonstrated a 2.5-fold increase of proliferation rates of left liver lobe segments subsequent to application of CD133+ bone marrow stem cells (BMSC) in addition to portal venous embolization of the right liver lobe. To gain insight in faith and mechanisms of CD133+BMSC applied to improve physiological liver regeneration processes 2D-cell co-culture models of CD133+BMSC with either primary liver cells or isolated sinusoidal endothelial cells (SEC) and 2 whole liver perfusion models will be utilized. In concert with a xenogeneic pre-clinical small animal model - analogue to our clinical concept – as well as clinical experimental studies, the potential of platelets and platelet derived microparticles (PMP) to promote CD133+BMSC participation in liver regeneration with consequent therapeutic options will be explored. In patients subsequent to liver resection, cytokines, growth factors and levels of platelet activation will be correlated with peripheral CD133+ cell mobilisation, levels of hepatic parenchymal loss and liver function and investigated for their capacity to modulate differentiation/ proliferation of CD133+BMSC in co-culture with primary liver cells. These studies will help to understand and improve a therapeutic concept using CD133+BMSC to promote liver regeneration. Beyond the surgical treatment of oncological patients with an indication for extensive partial hepatectomy the findings derived from these studies may have an impact on therapeutic promotion of organ regeneration following other scenarios of acute and chronic liver damage.

在8例计划进行扩大右肝切除术的患者中，采用新概念促进肝再生的初步临床经验表明，除了右肝叶门静脉栓塞外，应用CD 133+骨髓干细胞（BMSC）后左肝叶节段的增殖率增加了2.5倍。为了深入了解CD 133 +BMSC应用于改善生理性肝再生过程的信念和机制，将使用CD 133 +BMSC与原代肝细胞或分离的窦状隙内皮细胞（SEC）的2D细胞共培养模型和2个全肝灌注模型。与异种临床前小动物模型（类似于我们的临床概念）以及临床实验研究相一致，将探索血小板和血小板衍生微粒（PMP）促进CD 133 +BMSC参与肝再生的潜力以及随后的治疗选择。在肝切除术后的患者中，细胞因子、生长因子和血小板活化水平将与外周CD 133+细胞动员、肝实质损失水平和肝功能相关，并研究其调节与原代肝细胞共培养的CD 133 +BMSC分化/增殖的能力。这些研究将有助于理解和改善使用CD 133 +BMSC促进肝再生的治疗概念。除了对有广泛部分肝切除指征的肿瘤患者进行手术治疗外，这些研究的结果可能对其他急性和慢性肝损伤情况下的器官再生治疗促进产生影响。

项目成果

CD39 Modulates Hematopoietic Stem Cell Recruitment and Promotes Liver Regeneration in Mice and Humans After Partial Hepatectomy

CD39 调节造血干细胞募集并促进部分肝切除术后小鼠和人类的肝脏再生

• DOI: 10.1097/sla.0b013e31826c3ec2
• 发表时间: 2013
• 期刊: Annals of Surgery
• 影响因子: 9
• 作者: M. Schmelzle;C. Duhme;W. Junger;S.D. Salhanick;Y. Chen;V. Toxavidis;E. Csizmadia;L. Han;S. Bian;G. Fürst;M. Nowak;S. J. Karp;W. T. Knoefel;J. Schulte Esch;S. C. Robson
• 通讯作者: S. C. Robson

Increased Plasma Levels of Microparticles Expressing CD39 and CD133 in Acute Liver Injury

• DOI: 10.1097/tp.0b013e318278d3cd
• 发表时间: 2013-01-15
• 期刊: TRANSPLANTATION
• 影响因子: 6.2
• 作者: Schmelzle, Moritz;Splith, Katrin;Robson, Simon C.
• 通讯作者: Robson, Simon C.