Zusammenfassung
Bei unterschiedlichen Lebererkrankungen wird seit einigen Jahren alternativ zur orthotopen Lebertransplantation die Hepatozytentransplantation als neuer experimenteller Therapieansatz untersucht. Neben dem kurativen Ansatz bei genetischen Stoffwechseldefekten (Hämophilie, familiäre Hypercholesterinämie, etc.) ist die Hepatozytentransplantation als Ü berbrückung der Wartezeit auf ein geeignetes Lebertransplantat angedacht. Präklinische Studien am Tiermodell konnten diesbezüglich zeigen, dass sich intraperitoneal, intraportal oder über die Empfängermilz infundierte Hepatozyten in der erkrankten Leber absiedeln. Dies ermöglicht sowohl die Korrektur verschiedener angeborener Stoffwechselerkrankungen als auch eine verbesserte Überlebensrate beim akuten Leberversagen. Erstmalig wurde 1992 in einer klinischen Studie an 10 Patienten die Transplantation isolierter Hepatozyten vorgenommen. Fox u. Mitarb. beschrieben 1998 die erfolgreiche Transplantation allogener Leberzellen bei einem Kind mit Crigler-Najjar-Syndrom. Im gleichen Zeitraum durchgeführte Studien von Strom et al. bzw. Bilir et al. belegen die erfolgreiche Leberzelltransplantation zur transienten Behandlung des akuten Leberversagens. Grundsätzliche Voraussetzung für die Durchführung der Hepatozytentransplantation ist eine ausreichende Zellzahl differenzierter Hepatozyten. Um den Einsatz isolierter humaner Leberzellen in der Klinik ermöglichen zu können, ist die Entwicklung einer In-vitro- Kulturtechnik erforderlich, die sowohl eine reproduzierbare und hinreichend genügende Zellteilungsrate in Hepatozyten zu induzieren vermag als auch den Erhalt der physiologischen Funktion der Zellen garantiert. In der Arbeit wird eine Übersicht über die verschiedenen Ansätze der Kultivierung humaner Hepatozyten gegeben sowie auf alternative Zellquellen (tierische Hepatozyten, immortalisierte Zelllinien humanen Ursprungs, fetale Zellen bzw. Stammzellen), die zur Hepatozytentransplantation verwendet werden könnten, eingegangen und diese evaluiert.
Abstract
Over the past few years, hepatocyte transplantation has been considered as an alternative method for orthotopic liver transplantation for the treatment of various liver diseases. Beside curative approach for genetic metabolic deficiences (familial hypercholesterolemia, hemophilia, etc.), it could be a useful tool for bridging the waiting period until an appropriate donor organ is obtained. In preclinical animal studies, hepatocytes injected intraperitoneally, intraportally or into the spleen settle down in the diseased liver. This enables genetic modification to correct inborn metabolic deficiences and improves survival in acute liver failure. In 1992, the first clinical transplantation of isolated hepatocytes in 10 patients was performed. In 1998, Fox and coworkers described the succesful transplantation of allogeneic liver cells in a child with Crigler-Najjar syndrome. Accomplished studies of Strom et al. resp. Bilir et al. of the same year proved the effectiveness of liver cell transplantation for transient treatment of acute liver failure. Prerequisite of this cell-based therapeutic strategy is a sufficient amount of highly differentiated hepatocytes, hence, a well established in-vitro cell-culture technique is necessary to yield a reproducible number of proliferating hepatocytes and to preserve the physiological cell function. This review discusses the different experimental approaches regarding the cultivation of human hepatocytes and also the use of alternative cell sources (like animal hepatocytes, immortalized cells of human origin, progenitor cells from fetal human liver/liver stem cells) for hepatocyte transplantation.
Schlüsselwörter
Hepatozytentransplantation - Stoffwechseldefekte - Hepatozyten-Kultursysteme - alternative Zellquellen - Stammzellen
Key words
Hepatocyte transplantation - metabolic deficiencies - hepatocyte culture systems - alternative cell sources - stem cells
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Dr. med. Kerstin Leckel
Klinik für Allgemein, Visceral- und Transplantationschirurgie · Charité, Campus Virchow-Klinikum · Universitätsklinikum · Medizinische Fakultät der Humboldt-Universität zu Berlin
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