Diabetes Mellitus impairs the bone regeneration capacity of mesenchymal stromal cell-based therapy

Abstract

Background Diabetes mellitus (DM) negatively impacts bone tissue, leading to bone loss and increased fracture risk. Many individuals need additional treatments, and therapy based on mesenchymal stromal cells (MSCs) represents a promising treatment for bone defects in patients with diabetes. Aims The present study explored the effects of interactions between MSCs from normoglycemic (NG-MSCs) and diabetic (DM-MSCs) donors on osteoblast differentiation and the effects of cell therapy using NG-MSCs on bone regeneration in defects created in diabetic rats. Methods After inducing DM with streptozotocin, we evaluated the morphometric parameters of rat femurs and the osteoblast differentiation of MSCs, as well as the effects of the interaction between NG-MSCs and DM-MSCs on their osteoblast differentiation. The efficacy of cell therapy was measured by evaluating the bone repair in calvarial defects of diabetic rats treated with local injections of either NG-MSCs or a vehicle. Results DM induced bone loss and impaired the osteoblast differentiation of MSCs, which was partially restored by NG-MSCs, while the bone formation observed in defects treated with NG-MSCs and the vehicle was similar. Conclusion These results indicate that the beneficial effect of NG-MSCs on DM-MSCs did not translate into enhanced bone repair, mainly due to a hostile environment created by hyperglycemia, which compromised the ability of MSCs to induce bone formation.