Endocrine Abstracts

Fractures in diabetic patients are slower to heal and have an increased risk for developing malunion as compared to non-diabetic individuals. Given the known deficiencies in diabetic progenitor cell number and differentiation capacity, it is reasonable to hypothesise the aetiology of diabetic fracture malunion is dysregulated progenitor function. Therefore, we investigated the therapeutic efficacy of locally administered non-diabetic human bone marrow derived mesenchymal stem cells (hMSCs) to support femoral fracture repair in a murine model of diabetes.

A dose escalation study was performed administering hMSCs directly to a femoral fracture in a murine model of diabetes. The effect of local hMSC administration on the diabetic condition was evaluated by weekly monitoring of mouse weight, blood glucose, and terminal levels of circulating HbA1c. No significant change in body weight, blood glucose, or HbA1c as a result of hMSC administration was observed throughout the 56-day study. Animals maintained their weight at 26–28 g, their blood glucose levels >13 mM and HbA1c levels of 10–15% regardless of treatment group. MicroCT analysis indicates an increase in bone volume, a statistically significant increase in bone mineral density and trabecular thickness and a statistically significant decrease in the ratio of bone surface area to bone volume in animals treated with hMSCs as compared to saline treated controls. Further, four point bending analysis demonstrated a statistically significant increase in ultimate stress and e-modulus of the reparative bone. Although, the local administration of hMSCs did not alter the organismal diabetic condition, treatment of the diabetic fracture with hMSCs resulted in enhanced mechanical integrity of de novo reparative bone.

Therefore, the local administration of non-diabetic hMSCs to diabetic fractures has the potential to enhance callus remodelling resulting in the deposition of higher quality reparative bone.

Disclosure: This work was supported by European Union Framework 7 Program HEALTH-F2-2012-305736.