|dc.description.abstracteng||Due to the decreasing number of organ transplants, their tolerability gains greater significance
for affected patients. Therefore, these patients are permanently depended on taking
immunosuppressive drugs, which have numerous side effects. One of those side
effects most commonly encountered in dental treatment, is gingival enlargement.
In this study, we thus analysed the effect of three prevalent immunosuppressants (cyclosporine,
tacrolimus and sirolimus) as singular factors on fibroblasts representing the
dominant celltype in the gingiva. In order to evaluate the potential of these immunosuppressants,
embryonic gingival mice were treated in different concentrations of cyclosporine,
tacrolimus and sirolimus. In addition, exposure times were altered and two
control groups were applied. In the first step of the present study design, the different
concentrations within one immunosuppressant were compared to each other and to the
control groups. In a second step, the three immunosuppressants were compared to each
other with regard to selected concentrations.
In detail, we tested the effect of the immunosuppressants on the number of cells and the
viability, the cell diameter and the amount of procollagen type I. Number of cells, viability
and cell diameter were explored using the cell counter CASY® Modell TT (Roche
Diagnostics GmbH, Roche Applied Science, Penzberg, Deutschland). Procollagen-type-
I was determined using an ELISA (Mouse Procollage Type I C-Terminal Propeptide,
BlueGene Biotech Co, Shanghai, China).
Our results show that sirolimus has a significant negative effect on the number of cells
and the viability after an exposure time of 48 and 72 hours (p < 0,05). For cyclosporine
and tacrolimus our data indicate no effect on the number of cells and their viability (p >
The comparison between the three immunosuppressants with regard to selected concentrations
revealed a significant difference between the sirolimus group and the two
other immunosuppressants after an exposure time of 48 und 72 hours (p < 0,05). The
number of cells and the viability of sirolimus treated cells were both significantly lower
as compared to the other two immunosuppressants. Comparing cyclosporine treated
cells with tacrolimus treated ones, no significant difference was found for both parameters
(p > 0,05).
The statistical analysis of the cell diameter and procollagen type I rarely showed significant
effects. Neither the comparison of different concentrations within one immunosuppressant,
nor contrasting the three immunosuppressants for selected concentrations
indicated any statistically significant effect. Only the cells treated with 150 ng/Well cyc!
losporine showed a significant increase in cell diameter compared with one control
group (DMSO-control) after an exposure time of 48 hours (p = 0,0347).
Overall, the results do not support the hypothesis assuming a positive effect of the tested
immunosuppressants on the number of cells, the viability, the cell diameter and the
amount of procollagen type I. In the present study design the immunosuppressants do
not show the potential to change embryonic gingival mice fibroblasts leading to the clinical
picture of gingival enlargement as singular factors. This may indicate that several
different factors are needed to induce gingival enlargement as reflected in the multifactorial
model of Seymour and Smith (1991). As a conclusion, future studies should contribute
to a better understanding of singular influencing factors on gingival fibroblasts in
order to prevent immunocompromised patients from drug-induced gingival enlargement
and the resulting consequences for their dental treatment.||de