Diabetes Mellitus Impairs the Bone Regeneration Capacity of Mesenchymal Stromal Cell-Based Therapy.

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.