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„Liver engineering“ als neue Quelle von Spenderorganen

Eine systematische Übersichtsarbeit

Liver engineering as a new source of donor organs

A systematic review

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Zusammenfassung

Hintergrund

„Organ engineering“ stellt eine neuartige Strategie zur Minderung des Organmangels dar. Darunter versteht man die Herstellung eines Gerüsts aus explantierten Organen durch Entfernung aller zellulären Bestandteile (Dezellularisierung) und die Besiedelung (Repopularisierung) des Organgerüsts, um ein funktionierendes Organ in vitro für die Transplantation zu generieren. Diese Technik wurde auch für die Leber angepasst („liver engineering“).

Ziel der Arbeit

Darlegung des aktuellen Stands der Forschung des „liver engineering“ und Beschreibung des daraus resultierenden Forschungsbedarfes für die Zukunft.

Material und Methoden

Systematischer Review entsprechend den PRISMA-Richtlinien: Literaturrecherche mittels PUBMED (Suchbegriffe: liver, decellularization), Sichtung und Auswahl der Arbeiten nach Relevanzkriterien (Dezellularisierung, Repopularisierung, Transplantation), Extraktion und kritische Bewertung der relevanten Angaben und Daten bezogen auf die Dezellularisierungs-, Repopularisierungs- und Transplantationsbedingungen

Ergebnisse

Die Dezellularisierung der Leber wurde erfolgreich in Kleintier- und Großtiermodellen gezeigt. Zur Repopularisierung wurden Hepatozyten, Stammzellen und hepatische Zelllinien verwendet. 7 Arbeiten berichteten über die erfolgreiche Transplantation von dezellularisierten bzw. repopularisierten Organgerüsten. Trotz dieser Erfolge gibt es einen erheblichen Forschungsbedarf zur Auswahl des Spenders, Optimierung des Dezellularisierungsverfahrens sowie zur Auswahl der Zelltypen und Etablierung der optimalen Bedingungen für die Repopularisierung. Bei der Repopularisierung müssen 3 Ziele erreicht werden: 1) Besiedelung der Matrix mit einer hinreichenden Zahl an parenchymatösen Zellen, 2) Reendothelialisierung des Gefäßbaums um die Versorgung der Parenchymzellen mit Sauerstoff und Nährstoffen zu ermöglichen und 3) die adäquate Reepithelialisierung des Gallengangs. Für die klinische Umsetzung muss ein geeignetes Transplantationsmodell zur Testung der Funktionsfähigkeit der Organkonstrukte gefunden werden.

Schlussfolgerungen

„Liver engineering“ unter Verwendung biologischer dezellularisierter Organgerüste stellt eine wissenschaftlich-technologische und ethische Herausforderung dar. Die bisherigen Ergebnisse zeigen das Potenzial dieser Strategie auf und lassen erwarten, dass die Generierung von Organen für die Transplantation auf diesem Wege in der Zukunft möglich sein wird.

Abstract

Background

Organ engineering is a new strategy to cope with the shortage of donor organs. A functional scaffold from explanted organs is prepared by removing all cellular components (decellularization) and the reseeding (repopulation) of the organ scaffold to generate a functional organ in vitro for transplantation. This technique was also applied to the liver (liver engineering).

Objectives

Outline of the current state of the art and resulting approaches for future research strategies.

Material and methods

Systematic review according to the PRISMA guidelines: a PubMed-based literature search (search terms liver, decellularization), selection of relevant articles based on predetermined criteria for relevance (e.g. decellularization, repopulation and transplantation), extraction and critical appraisal of data and results concerning the conditions for decellularization, repopulation and transplantation.

Results

Decellularization was successfully performed in small and large animal models. Hepatocytes as well as stem cells and hepatic cell lines were applied for repopulation and 7 publications could show the successful transplantation of acellular and repopulated organ scaffolds. The current scientific need for further studies concerning the source of donor organs, optimization of the decellularization process, the cell type for the reseeding process and the establishment of the optimal conditions for the repopulation of the scaffold is still tremendous. For successful recellularization of the liver three goals need to be achieved: (1) reseeding of the organ scaffold with a sufficient amount of parenchymal cells, (2) endothelialization of the vascular tree to ensure the supply of oxygen and nutrients to parenchymal cells and (3) an appropriate epithelialization of the biliary tree. In order to progress to clinical trials a suitable transplantation model to verify the function of the organ constructs must be established.

Conclusion

Liver engineering using biological cell-free organ scaffolds represents a scientific and ethical challenge. The existing results emphasize the potential of this new and promising strategy to create organs for transplantation in the future.

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Authors and Affiliations

  1. Experimentelle Transplantationschirurgie, Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Drackendorfer Straße 1, 07747, Jena, Deutschland

    F. Mußbach &  U. Dahmen

  2. Institut für Pathologie, Dr. Panofsky-Haus, Klinikum Chemnitz gGmbH, Chemnitz, Deutschland

    O. Dirsch

  3. Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland

    U. Settmacher

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  1. F. Mußbach
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Correspondence to U. Dahmen.

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Mußbach, F., Dahmen, U., Dirsch, O. et al. „Liver engineering“ als neue Quelle von Spenderorganen. Chirurg 87, 504–513 (2016). https://doi.org/10.1007/s00104-015-0015-y

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