F Mußbach1, U Dahmen2, O Dirsch3, U Settmacher4. 1. Experimentelle Transplantationschirurgie, Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Drackendorfer Straße 1, 07747, Jena, Deutschland. 2. Experimentelle Transplantationschirurgie, Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Drackendorfer Straße 1, 07747, Jena, Deutschland. uta.dahmen@med.uni-jena.de. 3. Institut für Pathologie, Dr. Panofsky-Haus, Klinikum Chemnitz gGmbH, Chemnitz, Deutschland. 4. Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland.
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.
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.
Entities:
Keywords:
Decellularization; Liver engineering; Organ engineering; Organ shortage; Repopulation
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