The effect of alcohol on rabbit bone marrow and on the differentiation of mouse bone marrow stromal cells was investigated. Alcohol was administered intragastrically at a dose of 10 mL/kg/day for 1 to 6 months. Alcohol induced a significant increase in serum lipid peroxides, triglyceride, and cholesterol, and a reduction in superoxide dismutase activity. Fatty infiltration in the liver and adipogenesis in bone marrow were found histologically after alcohol administration. Fat cell hypertrophy and proliferation and diminished hematopoiesis in the subchondral area of the femoral head were observed. Triglycerides were deposited in osteocytes, which became pyknotic, and the percentage of empty osteocyte lacunae increased. None of these abnormal changes were detectable in the control group. In the in vitro study, the marrow stromal cells were treated with increasing (0.03, 0.09, and 0.15 mol/L) concentrations of ethanol for 4 to 21 days. Alcohol induced the differentiation of the cells into adipocytes. The number of adipocytes increased with longer durations of exposure to ethanol and with higher concentrations. Cells treated with ethanol also showed diminished alkaline phosphatase activity and expression of osteocalcin. These novel findings indicate that alcohol can directly induce adipogenesis, decrease osteogenesis in bone marrow stroma, and produce intracellular lipid deposits resulting in the death of osteocytes, which may be associated with the development of osteonecrosis, especially in patients with long-term and excessive use of alcohol.
Maximized specific loss power and intrinsic loss power approaching theoretical limits for alternating-current (AC) magnetic-field heating of nanoparticles are reported. This is achieved by engineering the effective magnetic anisotropy barrier of nanoparticles via alloying of hard and soft ferrites. 22 nm Co Mn Fe O /SiO nanoparticles reach a specific loss power value of 3417 W g at a field of 33 kA m and 380 kHz. Biocompatible Zn Fe O /SiO nanoparticles achieve specific loss power of 500 W g and intrinsic loss power of 26.8 nHm kg at field parameters of 7 kA m and 380 kHz, below the clinical safety limit. Magnetic bone cement achieves heating adequate for bone tumor hyperthermia, incorporating an ultralow dosage of just 1 wt% of nanoparticles. In cellular hyperthermia experiments, these nanoparticles demonstrate high cell death rate at low field parameters. Zn Fe O /SiO nanoparticles show cell viabilities above 97% at concentrations up to 500 µg mL within 48 h, suggesting toxicity lower than that of magnetite.
Current clinical therapies for critical-sized bone defects (CSBDs) remain far from ideal. Previous studies have demonstrated that engineering bone tissue using mesenchymal stem cells (MSCs) is feasible. However, this approach is not effective for CSBDs due to inadequate vascularization. In our previous study, we have developed an injectable and porous nano calcium sulfate/alginate (nCS/A) scaffold and demonstrated that nCS/A composition is biocompatible and has proper biodegradability for bone regeneration. Here, we hypothesized that the combination of an injectable and porous nCS/A with bone morphogenetic protein 2 (BMP2) gene-modified MSCs and endothelial progenitor cells (EPCs) could significantly enhance vascularized bone regeneration. Our results demonstrated that delivery of MSCs and EPCs with the injectable nCS/A scaffold did not affect cell viability. Moreover, co-culture of BMP2 gene-modified MSCs and EPCs dramatically increased osteoblast differentiation of MSCs and endothelial differentiation of EPCs in vitro. We further tested the multifunctional bone reconstruction system consisting of an injectable and porous nCS/A scaffold (mimicking the nano-calcium matrix of bone) and BMP2 genetically-engineered MSCs and EPCs in a rat critical-sized (8 mm) caviarial bone defect model. Our in vivo results showed that, compared to the groups of nCS/A, nCS/A+MSCs, nCS/A+MSCs+EPCs and nCS/A+BMP2 gene-modified MSCs, the combination of BMP2 gene -modified MSCs and EPCs in nCS/A dramatically increased the new bone and vascular formation. These results demonstrated that EPCs increase new vascular growth, and that BMP2 gene modification for MSCs and EPCs dramatically promotes bone regeneration. This system could ultimately enable clinicians to better reconstruct the craniofacial bone and avoid donor site morbidity for CSBDs.
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