The effects of combined low level laser therapy and mesenchymal stem cells on bone regeneration in rabbit calvarial defects

Abstract: This study evaluated the effect of Low Level Laser Therapy (LLLT) and Mesenchymal Stem Cells (MSCs) on bone regeneration. Background data: Although several studies evaluated the effects of MSCs and LLLT, there is little information available regarding in vivo application of LLLT in conjunction with MSCs. Methods: Forty-eight circular bone defects (6 mm in diameter) were prepared in the calvaria of 12 New- Zealand white rabbits. The defects of each animal were randomly assigned to 4 groups: (C) no treatment; (L) applying LLLT; (SC) filled with MSCs; (SCL) application of both MSCs and LLLT. LLL was applied on alternate days at wavelength of 810 nm, power density of 0.2 W/cm2 and a fluency of 4 J/cm2 using a Gallium–Aluminum–Arsenide (GaAlAs) diode laser. The animals were sacrificed after 3 weeks and then histological samples were evaluated to determine the amount of new bone formation and the remaining scaffold and inflammation. Results: The histological evaluation showed a statistically significant increase in new bone formation of LLLT group relative to the control and the other two experimental groups (p < 0.05). There was no significant difference in bone formation of the control group compared to experimental groups filled with MSCs. Laser irradiation had no significant effect on resorption of the scaffold material. In addition, inflammation was significantly reduced in LLLT group compared to the control defects and the other two experimental groups. Conclusion: Low level laser therapy could be effective in bone regeneration but there is no evidence of a synergistic effect when applied in conjunction with MSCs

A Roadmap for the Production of a GMP-Compatible Cell Bank of Allogeneic Bone Marrow-Derived Clonal Mesenchymal Stromal Cells for Cell Therapy Applications

Background: Allogeneic mesenchymal stromal cells (MSCs) have been used extensively in various clinical trials. Nevertheless, there are concerns about their efficacy, attributed mainly to the heterogeneity of the applied populations. Therefore, producing a consistent population of MSCs is crucial to improve their therapeutic efficacy. This study presents a good manufacturing practice (GMP)-compatible and cost-effective protocol for manufacturing, banking, and lot-release of a homogeneous population of human bone marrow-derived clonal MSCs (cMSCs). Methods: Here, cMSCs were isolated based on the subfractionation culturing method. Afterward, isolated clones that could reproduce up to passage three were stored as the seed stock. To select proliferative clones, we used an innovative, cost-effective screening strategy based on lengthy serial passaging. Finally, the selected clones re-cultured from the seed stock to establish the following four-tired cell banking system: initial, master, working, and end of product cell banks (ICB, MCB, WCB, and EoPCB). Results: Through a rigorous screening strategy, three clones were selected from a total of 21 clones that were stored during the clonal isolation process. The selected clones met the identity, quality, and safety assessments criteria. The validated clones were stored in the four-tiered cell bank system under GMP conditions, and certificates of analysis were provided for the three-individual ready-to-release batches. Finally, a stability study validated the EoPCB, release, and transport process of the frozen final products. Conclusion: Collectively, this study presents a technical and translational overview of a GMP-compatible cMSCs manufacturing technology that could lead to the development of similar products for potential therapeutic applications. Graphical Abstract: [Figure not available: see fulltext.

Effects of Photobiomodulation and Mesenchymal Stem Cells on Articular Cartilage Defects in a Rabbit Model

Objective: The aim of this study was to evaluate the effectiveness of the application of cultured autologous bone marrow mesenchymal stem cells (BMSCs) with scaffold and low-level laser therapy (LLLT) on the repair of articular cartilage defects in rabbits. Background data: For healing of the articular cartilage defects, although positive effects of BMSCs and LLLT have been demonstrated, their combination effect is still unknown; therefore, we investigated combining these two techniques has a synergistic effect. Materials and methods: After bone marrow aspiration from 10 rabbits, BMSCs were isolated, cultured in monolayer, suspended on a type I collagen scaffold and then implanted onto a full-thickness osteochondral defect (4 mm in diameter), artificially made on the patellar groove of both knees in the same rabbits. Then a knee was selected randomly in each rabbit as the experimental group, and subjected to Ga-Al-As (810 nm) laser irradiation with energy density of 4 J/cm2 every other day for 3 weeks. As the control group, the other knee did not receive LLLT. After this period, animals were euthanized and osteochondral defects were evaluated by histomorphometric methods. Results: No significant difference in new cartilage formation and inflammation was found between the groups (p > 0.05). However, there was significantly more new bone formation in the experimental group (p < 0.05). Conclusions: In terms of our research, although better healing in osteochondral defects was seen when combining BMSCs and LLLT compared with the use of BMSCs alone, this improvement was predominantly caused by new bone formation rather than new cartilage formation. © 2016, Mary Ann Liebert, Inc

Regional ionospheric mapping and modelling over Antarctica

The performance of regional and global models has been investigated when applied for long term mapping of ionospheric characteristics and modelling the Total Electron Content in the polar cap over an Antarctic region. Comparison results between modelled data and a short period of experimental values available for low solar activity in December 1993 and January 1994 are presented and discussed

Impact of Above-Average Proanabolic Nutrients Is Overridden by High Protein and Energy Intake in the Muscle-Tendon Unit Characteristics of Middle- to Older-Aged Adults

Background: The impact, within a single cohort, of independent modulators of skeletal muscle quality, including age, adiposity/obesity, habitual nutritional intake and physical activity (PA), is unclear. Objective: We examined the bivariate associations between age, adiposity, habitual nutritional intake and PA against 11 key intrinsic muscle-tendon unit (MTU) characteristics to identify the strongest predictors. We also compared overall profile differences between MTU categories using Z-scores illustrated in radar graphs. Method: Fifty untrained independent living males (n=15) and females (n=35) aged 43-80yrs (Mean±SD: 64±9yrs) were categorized by adiposity (Male: normal adiposity (NA) <28%; high adiposity (HA) ≥28%; Female: NA<40%; F HA≥40%) and BMI (Normal: BMI 18–<25; Overweight: BMI ≥25–<30; and Obese: BMI ≥ 30). Group differences were examined by body composition assessed using dual energy X-ray absorptiometry, habitual nutritional intake through a 3-day food diary, PA (work, leisure, sport) using the Baecke questionnaire, 14 serum cytokine concentrations using multiplex luminometry and 11 MTU characteristics of the gastrocnemius medialis using a combination of isokinetic dynamometry, electromyography, and ultrasonography. Results: Interestingly, classification by BMI highlighted differences between normal and obese individuals in 6/11 MTU characteristics (P<0.001-P=0.043). No statistical differences were reported in serum cytokine concentrations between adiposity/BMI classifications. BMI predicted 8/11 (r=0.62-0.31; P<0.001-P=0.032), daily energy intake predicted 7/11 (r=0.45-0.34; P=0.002-P=0.036), age predicted 5/11 (r=-0.49--0.32; P<0.001-P=0.032), work-based PA predicted 5/11 (r=0.43-0.32; P=0.003-P=0.048) and adiposity predicted 4/11 (r=0.51-0.33; P<0.001-P=0.022) MTU characteristics. Mathematical Z-scores and radar graphs illustrated how endocrine and dietary profiles but not PA differed between top and bottom ~20% muscle unit size and specific force. Conclusion: Given the number of factors associated with the MTU, education should be targeted to both adequate food quantity and quality (especially protein intake) and increasing habitual moderate to vigorous PA, whilst decreasing sedentary behavior. Specific endocrine parameters are also proposed as key pharmaceutical targets