Diabetes mellitus impairs the bone regeneration capacity of mesenchymal stem cell-based therapy

Abstract BACKGROUND Diabetes mellitus (DM) negatively impacts bone tissue, leading to bone loss and increased fracture risk with many in need of additional treatments, and therapy based on mesenchymal stem cells (MSCs) represents a promising treatment for bone defects in patients with diabetes. The present investigation explored the interactions between MSCs from normoglycemic (NG-MSCs) and diabetic (DM-MSCs) donors on osteoblast differentiation and the effects of NG-MSCs on bone regeneration in defects created in diabetic rats. METHODS After DM induction with streptozotocin, we evaluated the morphometric parameters of femurs and MSC osteoblast differentiation, as well as the effects of the interactions between NG-MSCs and DM-MSCs on osteoblast differentiation. The efficacy of cell therapy was measured by evaluating bone regeneration in the calvarial defects of diabetic rats treated with local injection of either NG-MSCs or vehicle. RESULTS DM induced bone loss and impaired osteoblast differentiation of MSCs, which was partially restored by NG-MSCs, and the bone formation observed in defects treated with either NG-MSCs or vehicle was similar. CONCLUSION These findings indicate that the beneficial effect of NG-MSCs on DM-MSCs did not translate to enhanced bone repair, mostly due to the hostile environment created by hyperglycemia, which compromises the capacity of MSCs to induce bone formation.