Adipose-Derived Stem Cells Combined With Inorganic Bovine Bone in Calvarial Bone Healing in Rats With Type 2 Diabetes

• Localización: Journal of periodontology, ISSN 0022-3492, Nº. 4, 2014, págs. 601-609
• Idioma: inglés
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• Resumen

  • Background: Clinical studies have revealed that patients with type 2 diabetes mellitus (DM) have higher implant and bone grafting failure rates than the general population, likely owing to inferior bone healing. The authors sought to investigate whether adipose-derived stem cells (ASCs) combined with inorganic bovine bone improves bone repair in calvarial vertical critical-sized defects (CSDs) in rats with type 2 DM.

    Methods: Bovine bone alone or seeded with 3 × 105, 3 × 106, or 3 × 107 ASCs/graft was randomly transplanted into calvarial CSDs in rats with DM induced by a high-fat diet with low-dose streptozotocin. Specimens were assayed using microcomputed tomography and histomorphometry at 4 and 8 weeks postimplantation.

    Results: The histologic results showed an increase in new bone formation in the experimental groups compared with the control group. Both bone volume/total volume and trabecular thickness of newly formed bone within CSDs were the highest, and trabecular spacing was the lowest, in the 3 × 106 group at 8 weeks for the most favorable outcome. The results showed that the amount of new bone was greatest in the 3 × 106 group by 8 weeks.

    Conclusions: ASCs enhanced vertical bone regeneration in calvarial defects in rats with type 2 DM, when used in association with bovine bone scaffolds. The findings suggest that a combination of ASCs and bovine bone scaffolds could improve bone quantity in vertical bone defects.

    Dental implantation has become the ideal method for restoring missing teeth.1 Diabetes mellitus (DM) is one of the most commonly encountered relative contraindications for dental implant therapy.2 With the prevalence of DM increasing dramatically worldwide, the number of individuals with missing teeth who will require dental implants is expected to grow.3 Patients with type 2 DM account for �90% to 95% of these cases.4 The major prerequisites for dental implants are adequate quality and quantity of bone in the alveolar ridge.5 Patients with type 2 DM with missing teeth often have vertical bone defects in the alveolar ridge. Of the methods that have been used to repair bone defects, autograft is regarded as the gold standard.6 However, autologous grafting has many limitations, such as additional surgeries to obtain bone grafts, morbidity at the donor sites, and difficulty in creating modifications that suit the defect areas.7 Moreover, DM is associated with numerous complications that increase the susceptibility of patients to surgical infection.8 So, the use of this type of grafting material is often precluded or discouraged in these patients. Several biomaterials such as allografts, xenografts, and alloplastic grafts are used for bone repair in alveolar vertical bone defects as alternatives to autografts,9 but the effect of bone healing is not as beneficial in patients with DM and missing teeth.10 Scaffolds loaded with growth factors have been used to enhance bone regeneration in bone defects in DM models.11 However, growth factors are generally expensive, which limits their use in clinical settings.12 Further, clinical studies have revealed higher bone grafting failure rates13 in patients with DM than the general population. Therefore, how to promote bone healing in alveolar bone vertical defects has been an issue of concern in patients with DM and missing teeth.

    Stem cell�based tissue engineering techniques have recently been suggested in the repair of bone defects, representing a new potential alternative for overcoming the disadvantages of autologous or allogeneic bone grafts.14 Compared with bone marrow stromal cells, adipose-derived stem cells (ASCs) are more easily obtained, are more abundant, and have less donor-associated morbidity. In addition, ASCs have multipotent and immunosuppressive abilities similar to those of stromal cells.15 ASCs have also been shown to promote the healing of critical-sized defects (CSDs) in the mandible16 and calvarium17,18 of several healthy species, when combined with appropriate scaffolds or carriers.15 ASCs have been used in cranium,19 maxilla, and mandible20 defects of healthy individuals to enhance bone healing in several studies. However, in type 2 DM models, the use of ASCs to repair CSDs has not been widely reported, and the effect of bone healing remains unknown.

    The model used here has already been applied in previous studies.12 The high-fat diet can lead to obesity, which itself can cause some degree of insulin resistance,4 and a low-dose streptozotocin regimen has been known to mildly impair the ß-cells in the pancreas, gradually resulting in hyperglycemia.12 The DM rat model induced by the enhanced diet, combined with a low dose of streptozotocin, is ideal for mimicking the natural history and metabolic characteristics of patients with DM.12,21 A CSD (diameter = 5 mm) was considered as the prototype model of an osseous non-union and discontinuity defect22 that could be used to evaluate the influence of any graft on bone healing.23 Herein, the authors evaluate the effects of ASCs combined with inorganic bovine bone on the healing of calvarial CSDs in DM rat models using a guided bone regeneration technique and assess the quantity of the newly formed bone relative to the density of the seeded cells.