Archives of Toxicology

, Volume 85, Issue 6, pp 607–612 | Cite as

Simple and quick method for whole-liver decellularization: a novel in vitro three-dimensional bioengineering tool?

  • Joery De Kock
  • Liesbeth Ceelen
  • Ward De Spiegelaere
  • Christophe Casteleyn
  • Paul Claes
  • Tamara Vanhaecke
  • Vera Rogiers
Toxicokinetics and Metabolism

Abstract

Proof of principle of organ reengineering through the development of a transplantable recellularized liver graft was published recently. As the decellularization time of the rat liver took 72 h, loss of some key matrix proteins seemed inevitable. Here, we describe the development of a three-dimensional naturally derived liver scaffold with an intact microvascular system that is capable of withstanding fluid flows in the three hepatic circular systems and that is obtained within 60 min. For this purpose, whole rat livers were sequentially perfused with a selection of mild tensioactive substances to remove the cellular components while preserving the major extracellular matrix proteins, including laminin, collagen I, collagen IV, and fibronectin. In addition, we could show the presence of extracellular matrix–bound growth factor islets, important for cell engraftment, migration, proliferation, and differentiation. This easy to prepare scaffold could represent a remarkable tool in the bioengineering of complex three-dimensional in vitro systems for advanced preclinical drug development.

Keywords

Liver matrix Organ decellularization Biological liver scaffold Three-dimensional scaffold 

Abbreviations

DLM

Decellularized liver matrix

ECM

Extracellular matrix

KHB

Krebs-Henseleit buffer

PBS

Phosphate-buffered saline

SEM

Scanning electron microscopy

SDS

Sodium dodecyl sulfate

3D

Three-dimensional

VEGF

Vascular endothelial growth factor

Notes

Acknowledgments

The authors thank Tatyana Doktorova, Jurgen De Craene, and Godelieve De Pauw for their excellent technical assistance.

Financial support

Joery De Kock is a doctoral research fellow of the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen). The research leading to these results has also received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement n°20161 (ESNATS) and from ISRIB (Brustem) and BELSPO (IAP).

Conflict of interest

The authors state that no conflict of interest is applicable to the presented work.

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Joery De Kock
    • 1
  • Liesbeth Ceelen
    • 1
  • Ward De Spiegelaere
    • 2
  • Christophe Casteleyn
    • 2
  • Paul Claes
    • 1
  • Tamara Vanhaecke
    • 1
  • Vera Rogiers
    • 1
  1. 1.Department of Toxicology, Center for Pharmaceutical ResearchVrije Universiteit Brussel (VUB)BrusselsBelgium
  2. 2.Department of Morphology, Faculty of Veterinary MedicineUniversiteit Gent (UGent)MerelbekeBelgium

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