Tissue Engineering der Leber

Zusammenfassung

Lebertransplantation ist bisher die einzige kurative Behandlungsmöglichkeit für Leberversagen im Endstadium. Limitierung der Lebertransplantation ist vor allem der Spenderorganmangel. Deshalb werden zellbasierte Behandlungsmöglichkeiten für bestimmte Lebererkrankungen derzeit intensiv beforscht. Prinzip des Tissue Engineering ist die Idee einer Wechselwirkung zwischen Zellen und einer dreidimensionalen Trägerstruktur (Matrix). Dabei bewirkt die Matrix durch eine dreidimensionale Orientierung der Zellen sowie eine gezielte Zell-Matrix Interaktion eine gezielte Stimulation von Wachstum und Differenzierung. In Hepatozytenkulturen konnte eine deutliche Steigerung des Zellanwachsens und des Zellüberlebens durch den Einsatz von dreidimensionalen Trägermaterialien und Bioreaktorsystemen gezeigt werden. Es zeigte sich auch eine deutlich gesteigerte Synthese- und Entgiftungsleistung der kultivierten Hepatozyten. Im Tiermodell wurde ein Modell der heterotopen Hepatozytentransplantation unter Nutzung dreidimensionaler Matrizes etabliert. In einem solchen Transplantationsmodell gelang der Nachweis eines Langzeitüberlebens und -funktion der transplantierten Hepatozyten. Limitierung war das unzureichende initiale Engraftment. Damit zeigt die Anwendung des Tissue Engineerings für die Leber vielversprechende Ergebnisse auf, um eine Weiterentwicklung zellbasierter Therapieformen für Lebererkrankungen zu ermöglichen. Lösungen für die Probleme einer adäquaten initialen Gefäßversorgung der transplantierten Zellen sowie der Formierung von Gallenwegen bedürfen zukünftiger Forschung, um das Tissue Engineering der Leber näher an einen klinischen Einsatz heranbringen zu können.

Abstract

Today liver transplantation is the only curative option for the treatment of end-stage liver diseases. A major limitation of liver transplantation is the donor organ shortage. Therefore, tissue engineering based cell transplantation is currently under investigation with the aim to replace liver tissue and function. The principle of tissue engineering is the notion of an interaction between a cell and a three-dimensional matrix. The matrix serves as a scaffold and guides a three-dimensional cell assembly. In addition, the matrix provides for a regulation of cell proliferation and function by cell-matrix interactions. In cultures of hepatocytes a regulation of cell proliferation and specific function by using three-dimensional matrices and by modifying the surface with isolated molecules of the extracellular matrix has been demonstrated. Furthermore, a beneficial effect of a flow bioreactor system on cell viability and function was observed. In addition, a system for heterotopic hepatocyte transplantation on polymeric matrices was developed in an animal model. In this transplantation model a long-term proliferation and function of transplanted hepatocytes was shown. The major limitation of matrix-based transplantation systems is the high initial cell loss, most probably due to an insufficient vascularisation. Thus, the development of vascularised matrices and the creation of bile ducts remain major problems in the technologies of hepatic tissue engineering and have to be addressed to enable further advances towards clinical applications.

Schlüsselwörter

Tissue Engineering der Leber - Leberzelltransplantation - Bioreaktorkultur - Polymermatrizes

Key words

hepatic tissue engineering - hepatocyte transplantation - bioreactor - polymer matrices

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