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.
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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
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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).
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The authors state that no conflict of interest is applicable to the presented work.
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De Kock, J., Ceelen, L., De Spiegelaere, W. et al. Simple and quick method for whole-liver decellularization: a novel in vitro three-dimensional bioengineering tool?. Arch Toxicol 85, 607–612 (2011). https://doi.org/10.1007/s00204-011-0706-1
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DOI: https://doi.org/10.1007/s00204-011-0706-1