This study aimed at characterizing the impact of type 2 diabetes mellitus (T2DM) on the bone marrow mesenchymal stem cell (BMMSC) secretome and angiogenic properties. BMMSCs from Zucker diabetic fatty rats (ZDF) (a T2DM model) and Zucker LEAN littermates (control) were cultured. The supernatant conditioned media (CM) from BMMSCs of diabetic and control rats were collected and analysed. Compared to results obtained using CM from LEAN‐BMMSCs, the bioactive content of ZDF‐BMMSC CM (i) differently affects endothelial cell (HUVEC) functions in vitro by inducing increased (3.5‐fold; P < 0.01) formation of tubule‐like structures and migration of these cells (3‐fold; P < 0.001), as well as promotes improved vascular formation in vivo, and (ii) contains different levels of angiogenic factors (e.g. IGF1) and mediators, such as OSTP, CATD, FMOD LTBP1 and LTBP2, which are involved in angiogenesis and/or extracellular matrix composition. Addition of neutralizing antibodies against IGF‐1, LTBP1 or LTBP2 in the CM of BMMSCs from diabetic rats decreased its stimulatory effect on HUVEC migration by approximately 60%, 40% or 40%, respectively. These results demonstrate that BMMSCs from T2DM rats have a unique secretome with distinct angiogenic properties and provide new insights into the role of BMMSCs in aberrant angiogenesis in the diabetic milieu.

Background To better understand bone fragility in type 2 diabetes mellitus and define the contribution of microcomputed tomography (micro-CT) to the evaluation of bone microarchitecture and vascularisation, we conducted an in vitro preliminary study on the femur of Zucker diabetic fatty (ZDF) rats and Zucker lean (ZL) rats. We first analysed bone microarchitecture, then determined whether micro-CT allowed to explore bone vascularisation, and finally looked for a link between these parameters. Methods Eight ZDF and six ZL rats were examined for bone microarchitecture (group 1), and six ZDF and six ZL rats were studied for bone vascularisation after Microfil® perfusion which is a radiopaque casting agent (group 2). In group 1, we used micro-CT to examine the trabecular and cortical bone microarchitecture of the femoral head, neck, shaft, and distal metaphysis. In group 2, micro-CT was used to study the blood vessels in the head, neck, and distal metaphysis. Results Compared to ZL rats, the ZDF rats exhibited significantly lower trabecular bone volume and number and higher trabecular separation in the three locations ( p = 0.02, p = 0.02, p = 0.003). Cortical porosity was significantly higher in the ZDF rats at the neck and shaft ( p = 0.001 and p = 0.005). We observed a dramatically poorer bone vascularisation in the femur of ZDF rats, especially in distal metaphysis ( p < 0.047). Conclusions Micro-CT demonstrated not only significant alterations in the bone microarchitecture of the femurs of ZDF rats, but also significant alterations in bone vascularisation. Further studies are required to demonstrate the causal link between poor vascularisation and impaired bone architecture.