Back to Search
Start Over
Primary human hepatocytes on biodegradable poly(l-lactic acid) matrices: a promising model for improving transplantation efficiency with tissue engineering.
- Source :
-
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society [Liver Transpl] 2011 Feb; Vol. 17 (2), pp. 104-14. - Publication Year :
- 2011
-
Abstract
- Liver transplantation is an established treatment for acute and chronic liver disease. However, because of the shortage of donor organs, it does not fulfill the needs of all patients. Hepatocyte transplantation is promising as an alternative method for the treatment of end-stage liver disease and as bridging therapy until liver transplantation. Our group has been working on the optimization of matrix-based hepatocyte transplantation. In order to increase cell survival after transplantation, freshly isolated human hepatocytes were seeded onto biodegradable poly(l-lactic acid) (PLLA) polymer scaffolds and were cultured in a flow bioreactor. PLLA discs were seeded with human hepatocytes and exposed to a recirculated medium flow for 6 days. Human hepatocytes formed spheroidal aggregates with a liver-like morphology and active metabolic function. Phase contrast microscopy showed increasing numbers of spheroids of increasing diameter during the culture period. Hematoxylin and eosin histology showed viable and intact hepatocytes inside the spheroids. Immunohistochemistry confirmed sustained hepatocyte function and a preserved hepatocyte-specific cytoskeleton. Albumin, alpha-1-antitrypsin, and urea assays showed continued production during the culture period. Northern blot analysis demonstrated increasing albumin signals. Scanning electron micrographs showed hepatocyte spheroids with relatively smooth undulating surfaces and numerous microvilli. Transmission electron micrographs revealed intact hepatocytes and junctional complexes with coated pits and vesicles inside the spheroids. Therefore, we conclude that primary human hepatocytes, precultured in a flow bioreactor on a PLLA scaffold, reorganize to form morphologically intact liver neotissue, and this might offer an optimized method for hepatocyte transplantation because of the expected reduction of the initial cell loss, the high regenerative potential in vivo, and the preformed functional integrity.<br /> (Copyright © 2011 American Association for the Study of Liver Diseases.)
- Subjects :
- Biomarkers metabolism
Bioreactors
Blotting, Northern
Cell Separation
Cell Shape
Cell Survival
Cells, Cultured
Fluorescent Antibody Technique
Hepatocytes metabolism
Hepatocytes ultrastructure
Humans
Immunohistochemistry
Microscopy, Electron, Scanning
Microscopy, Electron, Transmission
Polyesters
Serum Albumin genetics
Serum Albumin metabolism
Time Factors
Urea metabolism
alpha 1-Antitrypsin metabolism
Absorbable Implants
Hepatocytes transplantation
Lactic Acid
Liver Regeneration
Polymers
Tissue Engineering methods
Tissue Scaffolds
Subjects
Details
- Language :
- English
- ISSN :
- 1527-6473
- Volume :
- 17
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
- Publication Type :
- Academic Journal
- Accession number :
- 21280182
- Full Text :
- https://doi.org/10.1002/lt.22200