[Frontiers in Bioscience E3, 581-590, January 1, 2011]

5-Azacytidine enhances proliferation in transplanted rat fetal epiglottis

Sandra Marinovic Kulisic1, Gordana Juric-Lekic2, Masa Vikic-Topic2, Vedran Lokosek2, Vedran Radujkovic2, Floriana Bulic-Jakus3, Ana Katusic3, Maja Vlahovic3, Ljiljana Serman3, Nino Sincic3

1University Department of Dermatology and Venereology, Zagreb University Hospital Center and School of Medicine, University of Zagreb, Croatia, 2Department of Histology and Embryology, School of Medicine University of Zagreb, Croatia, 3Department of Biology, School of Medicine University of Zagreb, Croatia


1. Abstract
2. Introduction
3. Materials and methods
3.1. Animals
3.2. Isolation and transplantation of epiglottises
3.3. Histology
3.4. Immunohistochemistry
3.5. Transmission electron microscopy
3.6. Stereology
4. Results
4.1. Progress in development between fetal and adult rat epiglottis in situ
4.2. Maturation of fetal epiglottis in transplants
4.3. 5-azacytidine enhances the expression of the proliferating cell nuclear antigen (PCNA) in transplants
5. Discussion
6. Acknowledgments
7. References


Fetal rat epiglottis and its developmental potential in ectopic transplants under the influence of the epigenetic drug was investigated. Epiglottises from 17-days-old rat embryos were transplanted under kidney capsules of adult rats for 14 days. 5-azacytidine (5mg/kg) was injected intraperitoneally during first three days and controls were sham treated. TEM, immunohistochemical detection and quantitative stereological analysis of the Proliferating Cell Nuclear Antigen (PCNA) expression (numerical density Nv) were performed. Typical chondroblasts with long surface processes and sparse lipid droplets were found in fetal epiglottis and chondrocytes with shorter processes, numerous lipid droplets and elastic fibers in adult. PCNA was expressed in almost all cells of the fetal epiglottis while in the adult it was expressed in minority of cells. In transplants, differentiation progressed towards the differentiation found in the adult. Application of 5-azacytidine increased the capacity for proliferation (Nv PCNA) in comparison to controls but no difference in differentiation was observed. Data about the developmental potential and induction of proliferation in mammalian epiglottis by epigenetic modulation is of importance for regenerative medicine.