Current concepts from diagnosis to management in Gorham–Stout disease: a systematic narrative review of about 350 cases

Patients with Gorham–Stout disease (GSD) present progressive destruction and resorption of bone. Typical bone-related symptoms include swelling, pain and functional impairment in the region involved. The three aspects of GSD etiopathology are osteoclasts, angiogenesis/lymphangiogenesis and osteoblast function. Multi-targeted pharmacological approach includes innovative options and represent milestones of treatment, sometimes associated with radiotherapy. Surgery is mainly used to treat complications: pathologic/impending fractures, spinal instability or deformities and chylothorax. In this narrative review, we highlight current standards in diagnosis, clinical management and therapeutic strategies.

Treatment of Radiation Bone Injury with Transplanted hUCB-MSCs via Wnt/β-Catenin

Radiation-induced bone injury (RIBI) is one of the complications after radiotherapy for malignant tumors. However, there are no effective measures for the treatment of RIBI in clinical practice, and the mechanism of RIBI is unclear. We use a single high-dose ionizing radiation (6Gy) to analyze the effect of radiotherapy on osteoblast function. Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) were cocultured with irradiated osteoblasts to examine their therapeutic effects and mechanisms on osteoblast injury. The hUCB-MSC transplantation mouse model is used to confirm the in vivo role of hUCB-MSC treatment in radiation bone injury. Western blot analysis, qRT-PCR, immunohistochemistry, and immunofluorescence staining were used to analyze gene expression and angiogenesis. The apoptosis and migration of osteoblasts were measured by Hoechst staining, scratch test, and transwell. The differentiation of osteoblasts was measured by ALP and Alizarin red staining and transmission electron microscopy. The bone-related parameters of mice were evaluated by micro-CT analysis. We found that radiation can damage the DNA of osteoblasts; induce apoptosis; reduce the differentiation, migration, and adhesion of osteoblasts, leading to lipogenesis of bone marrow mesenchymal stem cells (BMSCs) and reducing the source of osteoblasts; and increase the number of osteoclasts in bone tissue, while MSC treatment prevents these changes. Our results reveal the inhibitory effect of radiation on osteoblast function. hUCB-MSCs can be used as a therapeutic target for the development of new therapeutic strategies for radiotherapy of bone injury diseases.

Enhancing osteoblast function through pulsed electrical stimulation: implications for peri-implant healing and osseointegration

Electrical stimulation has been suggested as a mean for promoting the bonding of bone tissue to an implant, known as osseointegration. Previous work has investigated the impact of electrical stimulation in different models, both in vitro and in vivo, using various electrode configurations for delivering the electric field and with a wide range of stimulation parameters. However, there is no consensus on optimal electrode configuration nor stimulation parameters. Here, we investigated a novel approach of delivering electrical stimulation to a titanium implant using parameters clinically tested in a different application, namely peripheral nerve stimulation. We propose an in vitro model comprising of Ti6Al4V implants precultured with MC3T3-E1 preosteoblasts, stimulated for 72 h at two different pulse amplitudes (10 µA and 20 µA) and at two different frequencies (50 Hz and 100 Hz). We found that pulsed electrical stimulation enhances cell viability (and/or proliferation) and collagen production in an approximately dose-dependent manner. Our findings suggest that pulsed electrical stimulation with characteristics similar to peripheral nervous stimulation has the potential to accelerate osteoblast function and may provide a promising approach to improving peri-implant bone healing, particularly to neuromusculoskeletal interfaces in which implanted electrodes are readily available.