Diabetic peripheral neurovascular diseases (DPNVs) are complex, lacking effective treatment. Autologous/allogeneic transplantation of adipose-derived stem cells (ADSCs) is a promising strategy for DPNVs. Nonetheless, the transplanted ADSCs demonstrate unsatisfying viability, migration, adhesion, and differentiation in vivo, which reduce the treatment efficiency. Netrin-1 secreted as an axon guidance molecule and served as an angiogenic factor, demonstrating its ability in enhancing cell proliferation, migration, adhesion, and neovascularization. ADSCs acquired from adipose tissue were modified by Netrin-1 gene (NTN-1) using the adenovirus method (N-ADSCs) and proliferation, migration, adhesion, and apoptosis examined under high-glucose condition. The sciatic denervated mice (db/db) with type 2 diabetes mellitus (T2DM) were transplanted with N-ADSCs and treatment efficiency assessed based on the laser Doppler perfusion index, immunofluorescence, and histopathological assay. Also, the molecular mechanisms underlying Netrin-1-mediated proliferation, migration, adhesion, differentiation, proangiogenic capacity, and apoptosis of ADSCs were explored. N-ADSCs improved the proliferation, migration, and adhesion and inhibited the apoptosis of ADSCs in vitro in the condition of high glucose. The N-ADSCs group demonstrated an elevated laser Doppler perfusion index in the ADSCs and control groups. N-ADSCs analyzed by immunofluorescence and histopathological staining demonstrated the distribution of the cells in the injected limb muscles, indicating chronic ischemia; capillaries and endothelium were formed by differentiation of N-ADSCs. The N-ADSCs group showed a significantly high density of the microvessels than the ADSCs group. The upregulation of AKT/PI3K/eNOS/P-38/NF-κB signaling pathways and secretion of multiple growth factors might explain the positive effects of Netrin-1 on ADSCs. The overexpression of Netrin-1 in ADSCs improves proliferation, migration, and treatment effect in type 2 diabetic mice with sciatic denervation, which directs the clinical treatment of patients with DPNVs.

Chronic inflammation mediated by artery infiltrated macrophages plays critical role in artery restenosis after endovascular therapy. Evidence has demonstrated the potential ability of photothermal therapy (PTT) in eliminating chronic inflammation by targeting inflammatory cells including macrophages. Recently, increasing attention has been payed to copper chalcogenide nanocrystals doped of radiocontrast agent, e.g., bismuth (Bi) for computed tomography (CT) guided PTT. However, the application of imaging guided PTT in preventing artery restenosis is lacking and limited. Herein, a novel multifunctional CuBiS₂ nanoparticles (CuBiS₂ NPs) were synthesized for CT imaging guided PTT in artery re-stenosis prevention. The optimum amount and other conditions of CuBiS₂ NPs were optimized to exert the maximum ablation effect on macrophages with good biocompatibility. In vivo carotid injury model revealed that CuBiS₂ NPs exhibited promising therapeutic effect on inhibition of artery stenosis by eliminating macrophages with excellent CT imaging ability. The recent study highlights a new cost-effective metal nanostructures-based nanotechnology in prevention of artery restenosis after endovascular therapy.