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肝组织工程的发展

Development of hepatic tissue engineering.

作者信息

Fiegel Henning Cornelius, Kneser Ulrich, Kluth Dietrich, Metzger Roman, Till Holger, Rolle Udo

机构信息

Department of Pediatric Surgery, Goethe-University of Frankfurt am Main, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany.

出版信息

Pediatr Surg Int. 2009 Aug;25(8):667-73. doi: 10.1007/s00383-009-2389-8. Epub 2009 Jun 2.

Abstract

Liver transplantation is still the only treatment for end-staged liver diseases in children. However, donor organ shortage and immunosuppression are major limitations. Thus, approaches of hepatocyte transplantation are under investigation. Using cells might permit mass expansion, cryopreservation, and the ex vivo genetic modification of cells. For the development of cell-transplantation techniques, the use of three-dimensional scaffolds as carrier was shown to be advantageous. Polymeric matrices permit the formation of a neo-tissue and stimulation by the modification of the matrix surface. Another important issue is to define the right cell type for transplantation. Adult hepatocytes have a limited growth and differentiation potential. In contrast, fetal liver cells (FLC) possess an enormous growth and a bipotential differentiation potential. Thus, these cells may be very attractive as a cell resource for developing cell-based liver replacement. A third major issue in this approach is the neo-vascularization. Therefore, the transplantation in a recently developed model using a microsurgically created arterioveno-venous (AV) loop as a central vessel for the neo-tissue was used for transplantation of FLC in a fibrin-matrix. Initial results indicated that the transplantation of FLC using the AV-loop transplantation model may be promising for the development of highly vascularized in vivo tissue-engineered liver support systems.

摘要

肝移植仍是治疗儿童终末期肝病的唯一方法。然而,供体器官短缺和免疫抑制是主要限制因素。因此,肝细胞移植方法正在研究中。使用细胞可能允许细胞的大规模扩增、冷冻保存和体外基因改造。对于细胞移植技术的发展,使用三维支架作为载体已显示出优势。聚合物基质允许形成新组织并通过基质表面修饰进行刺激。另一个重要问题是确定合适的移植细胞类型。成体肝细胞的生长和分化潜力有限。相比之下,胎儿肝细胞(FLC)具有巨大的生长和双能分化潜力。因此,这些细胞作为开发基于细胞的肝替代物的细胞资源可能非常有吸引力。这种方法的第三个主要问题是新生血管形成。因此,在最近开发的一个模型中进行移植,该模型使用显微外科创建的动静脉(AV)环作为新组织的中央血管,用于将FLC移植到纤维蛋白基质中。初步结果表明,使用AV环移植模型移植FLC可能有望开发高度血管化的体内组织工程肝支持系统。

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