ABSTRACT
Control over endogenous reparative mechanisms is the future of regenerative medicine. The rabbit ear defect is a rare model which allows the observation of the epimorphic regeneration of elastic cartilage. However, the mechanisms of phenotypical restoration of this highly differentiated tissue have not been studied. We modelled circular ear defects of different sizes (4, 6, and 8 mm in diameter) in 12 laboratory rabbits, and observed them during 30, 60, 90, and 120 day periods. Excised tissues were processed and analyzed by standard histological methods and special histochemical reactions for senescence associated-ß-galactosidase and lectin markers. We demonstrated that larger defects caused significant elevation of senescence associated-ß-galactosidase in chondrocytes. The fullness of epimorphic regeneration of elastic cartilage depended on the activation of cellular senescence and synthesis of elastic fibers. Further investigation into the role of cells with senescence-associated secretory phenotype in damaged tissues can present new targets for controlled tissue regeneration.
ABSTRACT
One of the severe complications occurring because of the patient's intubation is tracheal stenosis. Its incidence has significantly risen because of the COVID-19 pandemic and tends only to increase. Here, we propose an alternative to the donor trachea and synthetic prostheses-the tracheal equivalent. To form it, we applied the donor trachea samples, which were decellularized, cross-linked, and treated with laser to make wells on their surface, and inoculated them with human gingiva-derived mesenchymal stromal cells. The fabricated construct was assessed in vivo using nude (immunodeficient), immunosuppressed, and normal mice and rabbits. In comparison with the matrix ones, the tracheal equivalent samples demonstrated the thinning of the capsule, the significant vessel ingrowth into surrounding tissues, and the increase in the submucosa resorption. The developed construct was shown to be highly biocompatible and efficient in trachea restoration. These results can facilitate its clinical translation and be a base to design clinical trials.
Subject(s)
COVID-19 , Tissue Engineering , Animals , Humans , Lasers , Mice , Pandemics , Rabbits , Tissue Engineering/methods , Tissue Scaffolds , TracheaABSTRACT
The possibility that binuclear dinitrosyl iron complexes with glutathione and cysteine (DNIC-GSÐ and B-DNIC-Cys) have a strong cytotoxic effect on the growth of endometrioid tumours (EMT) in rats with surgically induced experimental endometriosis established in our previous studies has been supported with experimental data. The increase in the DNIC-GSÐ or B-DNIC-Cys dose from 10 (in our previous studies) to 20 µmol/kg (after i/p administration to experimental rats) fully suppressed the growth of uterine tissues implanted onto the inner surface of the abdominal wall. At 2 µmol/kg DNIC-GSÐ, the median value of EMT volume increased from 0 to 15 mm3, while the mean size of EMT-from 55 to 77 mm3 (data from EMT measurements in 10 experimental rats). After treatment of animals with B-DNIC with N-acetyl-L-cysteine (10 µmol/kg) known for its ability to penetrate easily through the cell membrane, the inhibiting effect on EMT growth diminished as could be evidenced from the transformation of ~30% of the implants into large-size EMT. Possible reasons for this phenomenon are discussed.
