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.

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