Osteoblast-Based Therapy-A New Approach for Bone Repair in Osteoporosis: Pre-Clinical Setting.

BACKGROUND: Osteoporosis is a metabolic bone disease characterized by low bone density resulting in increased fracture susceptibility. This research was constructed to uncover the potential therapeutic application of osteoblasts transplantation, generated upon culturing male rat bone marrow-derived mesenchymal stem cells (BM-MSCs) in osteogenic medium (OM), OM containing gold (Au-NPs) or gold/hydroxyapatite (Au/HA-NPs) nanoparticles, in ovariectomized rats to counteract osteoporosis. METHODS: Forty rats were randomized into: (1) negative control, (2) osteoporotic rats, whereas groups (3), (4) and (5) constituted osteoporotic rats treated with osteoblasts yielded from culturing BM-MSCs in OM, OM plus Au-NPs or Au/HA-NPs, respectively. After 3 months, osterix (OSX), bone alkaline phosphatase (BALP), sclerostin (SOST) and bone sialoprotein (BSP) serum levels were assessed. In addition, gene expression levels of cathepsin K, receptor activator of nuclear factor-κb ligand (RANKL), osteoprotegerin (OPG) and RANKL/OPG ratio were evaluated using real-time PCR. Moreover, histological investigation of femur bone tissues in different groups was performed. The homing of implanted osteoblasts to the osteoporotic femur bone of rats was documented by Sex determining region Y gene detection in bone tissue. RESULTS: Our results indicated that osteoblasts infusion significantly blunted serum BALP, BSP and SOST levels, while significantly elevated OSX level. Also, they brought about significant down-regulation in gene expression levels of cathepsin K, RANKL and RANKL/OPG ratio versus untreated osteoporotic rats. Additionally, osteoblasts nidation could restore bone histoarchitecture. CONCLUSION: These findings offer scientific evidence that transplanting osteoblasts in osteoporotic rats regains the homeostasis of the bone remodeling cycle, thus providing a promising treatment strategy for primary osteoporosis.

Exploiting bilosomes for delivering bioactive polysaccharide isolated from Enteromorpha intestinalis for hacking hepatocellular carcinoma.

Bile salts containing vesicles (bilosomes) represent a portentous vesicular carrier that showed prosperous results in delivering active moieties in the gastrointestinal tract (GIT). In this study, bilosomes were exploited to deliver sulfated polysaccharide-protein complexes of Enteromorpha intestinalis (EHEM) and enhance its activity against hepatocellular carcinoma as well as resist harsh GIT conditions. Bilosomes were prepared using the sodium salt of three different bile acids (cholic, deoxycholic, taurodeoxycholic) and two different nonionic surfactants (Span 40 and 65). The effects of experimental variables were thoroughly studied to obtain an optimum formulation loading EHEM. The selected formulation (EH-Bilo-2) prepared with sodium cholate and Span 65 displayed nano-sized (181.1 ± 16.80 nm) spherical vesicles with reasonable entrapment efficiency (71.60 ± 0.25%) and controlled release properties; and thus was investigated as anti-hepatocarcinogenic candidate for in vivo studies. Treatment of hepatocellular carcinoma (HCC) bearing rats with EH-Bilo-2 experienced significant decrease in serum α-fetoprotein, endoglin, lipocalin-2, and heat shock protein 70 levels vs. the untreated counterparts. Furthermore, the photomicrographs of their liver tissue sections showed focal area of degenerated pleomorphic hepatocytes with fine fibrosis originating from the portal area. Thus, the optimized bilosomal formulation is a promising delegate for tackling hepatocellular carcinoma owing to its powerful anti-cancer and anti-angiogenic activity.