Embryonic porcine liver as a source for transplantation: advantage of intact liver implants over isolated hepatoblasts in overcoming homeostatic inhibition by the quiescent host liver
| Autor: | Helena Katchman, Orna Tal, Enrique Freud, Elias Shezen, Gil Hecht, Yair Reisner, Sivan Cohen, Alexander Shtabsky, Dalit Tchorsh, Anna Aronovich, Benjamin Dekel, Smadar Eventov-Friedman |
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| Rok vydání: | 2008 |
| Předmět: |
Swine
Xenotransplantation medicine.medical_treatment Transplantation Heterologous Spleen Cell Separation Mice SCID Biology Cell therapy Andrology Mesoderm Mice medicine Animals Homeostasis RNA Messenger Cell Proliferation Liver injury Fetus Stem Cells Cell Differentiation Epithelial Cells Cell Biology medicine.disease Liver Transplantation Transplantation medicine.anatomical_structure Gene Expression Regulation Liver Immunology Hepatic stellate cell Hepatocytes Molecular Medicine Fetal pig Developmental Biology |
| Zdroj: | Stem cells (Dayton, Ohio). 26(5) |
| ISSN: | 1549-4918 |
| Popis: | Cell therapy as an alternative to orthotopic liver transplantation represents a major challenge, since negligible proliferation of isolated hepatocytes occurs after transplantation because of the stringent homeostatic control displayed by the host liver. Thus, different modalities of liver injury as part of the pretransplant conditioning are a prerequisite for this approach. The major objective of the present study was to test whether xenotransplantation of pig fetal liver fragments, in which potential cell-cell and cell-stroma interactions are spared, might afford more robust growth and proliferation compared with isolated pig fetal hepatoblasts. After transplantation into SCID mice, fetal liver tissue fragments exhibited marked growth and proliferation, in the setting of a quiescent host liver, compared with isolated fetal hepatoblasts harvested at the same gestational age (embryonic day 28). The proliferative advantage of fetal pig liver fragments was clearly demonstrated by immunohistochemical and morphometric assays and was observed not only after implantation into the liver but also into extrahepatic sites, such as the spleen and the subrenal capsule. The presence of all types of nonparenchymal liver cells that is crucial for normal liver development and regeneration was demonstrated in the implants. Preservation of the three-dimensional structure in pig fetal liver fragments enables autonomous proliferation of transplanted hepatic cells in the setting of a quiescent host liver, without any requirement for liver injury in the pretransplant conditioning. The marked proliferation and functional maturation exhibited by the pig fetal liver fragments suggests that it could afford a preferable source for transplantation. Disclosure of potential conflicts of interest is found at the end of this article. |
| Databáze: | OpenAIRE |
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