Bone Marrow-Derived Stem Cells as a Cytotherapy for Sirolimus-Induced Periodontal Ligament and Alveolar Bone Injury in a Rat Model

Abstract

Background: Sirolimus is known to be the most common immunosuppressive and anti-cancer drug regardless to its adverse side effects. Bone marrow derived -mesenchymal cells represent a great interest, particularly in the areas of regenerative medicine. Aim of the study: The current research aimed to examine the efficacy of stem cell transplantation for treating the periodontal ligament and alveolar bone affection that caused by Sirolimus.Materials and methods: Fifty male albino rats with average body weight 200-250 gram were used in this investigation. The animals were divided into the following groups: Group I: 20 rats served as controls and subdivided into 2 subgroups 10 animals each: Group I.1: Using a curved metallic oral gavage, ethanol and saline were given in a daily oral dose of 10 mg/kg body weight to Group I.1 for 3 months. Group I.2: treated with the same way as group I.1 then left untreated for 2 weeks Group II: 20 animals subdivided into 2 subgroups, 10 animals each: Group II.1 (Sirolimus group) treated with immunosuppressive drug (Rapamycin) dissolved in ethanol and saline in a daily oral dose of 10 mg/kg body weight using a curved metallic oral gavage for 3 months. Group II.2: (Recovery group) treated with the same dose and route of administration of group II.1 for 3 months then left untreated for 2 weeks as a recovery period. Group III: 10 rats treated with the same dose of Rapamycin in group II then injected by a single intravenous infusion of mesenchymal bone marrow stem cells. For bone marrow- mesenchymal cells isolation and culture, ten adult male albino rats were used as a source of bone marrow. At the end of experiment, the rats were sacrificed, the jaws of rats were dissected out and processed to be stained with: Hematoxylin and eosin staining for histological examination. Streptavidin-biotin immunohistochemical method for Vimentin and CD44 localization for stem cells characterization and homing detection respectively and streptavidin-biotin immunohistochemical method of Bcl2 for anti-apoptotic expression detection. Results: Sirolimus showed dramatic degenerative changes on the periodontal ligaments and alveolar bone, however the transplanted stem cell helped tissues to partially retain their texture and accelerate their healing. Conclusion Sirolimus caused severe adverse effects on the periodontal ligaments and alveolar bone which did not resolved after recovery period of 2 weeks, however, the degeneration was more dramatic. Interestingly, bone marrow- derived stem cells transplantation represented a promising attempt to overcome the Sirolimus drawbacks.