Uso de la terapia (células madre mesenquimales de la médula osea y células madre mesenquimales de la bola adiposa de Bichat) en materiales biocerámicos para la regeneración ósea de la sínfisis mandibular de ratas sanas, diabéticas, osteoporóticas y diabéticas con osteoporosis

Abstract

Background: crititcal-sized bone defects (CSBDs) can hamper functional and aesthetic treatment with dental implants in healthy patients. Systemic diseases such as diabetes or osteoporosis can further complicate the regeneration of CSBDs. For that reason, bone marrow mesenchymal stem cells (BMSCs) and buccal fat pad mesenchymal stem cells (BFPSCs) cultivated in biomateriales may be useful. Objective: to compare new bone formation in rat mandibular symphysis critical-sized defects (CSBDs) in healthy, diabetics, osteoporotics, and diabetics-osteoporotics rats filled with bioceramics (BCs) with or without bone marrow mesenchymal stem cells (BMSCs) and buccal fat pad mesenchymal stem cells (BFPSCs). Materials and Methods: A total of 96 adult female Sprague-Dawley rats were randomized into four groups (n=24 per group): Group 1 healthy, Group 2 diabetics, Group 3 osteoporotics, and Group 4 diabetics-osteoporotics rats. Streptozotocin was used to induce type 1 diabetes in Group 2 and 4, while bilateral ovariectomy was used to induce osteoporosis in Group 3 and 4. The central portion of the rat mandibular symphysis was used as a physiological CSBD. In each group, eight defects were filled with BCs (hydroxypatatite 60% and β-tricalcium phosphate 40%) alone, another eight with BMSCs cultured on BCs and the remaining eight were filled with BCs and BFPSCs. The animals were sacrificed at 4 and 8 weeks, and the mandibles were processed for micro-computed tomography to analyze radiological union and bone mineral density (BMD); histological analysis of the bone union; and immunohistochemical analysis, which included immunoreactivity of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2). Results: In all groups (healthy, diabetics, osteoporotics, and diabetics-osteoporotics), the CSBDs filled with BCs + BFPSCs showed greater radiological bone union, BMD, histological bone union, and more VEGF and BMP-2 positivity than those CSBDs treated with BCs + BMSCs and, in turn, this last revealed higher values than those treated with BCs alone (at 4 and 8 weeks) with statistically significant differences. Conclusions: Application of BFPSCs cultured on biphasic BCs improves bone regeneration in CSBDs compared with treatment of BMSCs with BCs and that those regenerated with biphasic BCs alone in healthy, diabetics, osteoporotics, and diabetics-osteoporotics rats. Clinical relevance: The results of this study can help the functional and aesthetic rehabilitation of healthy, diabetic, ostoeoporotic and, above all, those who manifest both diseases concomitantly; although future studies will be necessary in order to have more scientific evidence