Application of Autologous Bone Marrow Derived Mesenchymal Stem Cells to an Ovine Model of Growth Plate Cartilage Injury

Injury to growth plate cartilage in children can lead to bone bridge formation and result in bone growth deformities, a significant clinical problem currently lacking biological treatment. Mesenchymal stem/stromal cells (MSC) offer a promising therapeutic option for regeneration of damaged cartilage, due to their self renewing and multi-lineage differentiation attributes. Although some small animal model studies highlight the therapeutic potential of MSC for growth plate repair, translational research in large animal models, which more closely resemble the human condition, are lacking. Our laboratory has recently characterised MSCs derived from ovine bone marrow, and demonstrated these cells form cartilage-like tissue when transplanted within the gelatin sponge, Gelfoam, in vivo. In the current study, autologous bone marrow MSC were seeded into Gelfoam scaffold containing TGF-β1, and transplanted into a surgically created defect of the proximal ovine tibial growth plate. Examination of implants at 5 week post-operatively revealed transplanted autologous MSC failed to form new cartilage structure at the defect site, but contributed to an increase in formation of a dense fibrous tissue. Importantly, the extent of osteogenesis was diminished, and bone bridge formation was not accelerated due to transplantation of MSCs or the gelatin scaffold. The current study represents the first work that has utilised this ovine large animal model to investigate whether autologous bone marrow derived MSC can be used to initiate regeneration at the injured growth plate

The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review.

BACKGROUND: The management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue engineering to improve the outcome for patients requiring cartilage repair. Many published reviews on cartilage repair only list human clinical trials, underestimating the wealth of basic sciences and animal studies that are precursors to future research. We therefore set out to perform a systematic review of the literature to assess the translation of stem cell therapy to explore what research had been carried out at each of the stages of translation from bench-top (in vitro), animal (pre-clinical) and human studies (clinical) and assemble an evidence-based cascade for the responsible introduction of stem cell therapy for cartilage defects. This review was conducted in accordance to PRISMA guidelines using CINHAL, MEDLINE, EMBASE, Scopus and Web of Knowledge databases from 1st January 1900 to 30th June 2015. In total, there were 2880 studies identified of which 252 studies were included for analysis (100 articles for in vitro studies, 111 studies for animal studies; and 31 studies for human studies). There was a huge variance in cell source in pre-clinical studies both of terms of animal used, location of harvest (fat, marrow, blood or synovium) and allogeneicity. The use of scaffolds, growth factors, number of cell passages and number of cells used was hugely heterogeneous. SHORT CONCLUSIONS: This review offers a comprehensive assessment of the evidence behind the translation of basic science to the clinical practice of cartilage repair. It has revealed a lack of connectivity between the in vitro, pre-clinical and human data and a patchwork quilt of synergistic evidence. Drivers for progress in this space are largely driven by patient demand, surgeon inquisition and a regulatory framework that is learning at the same pace as new developments take place

Bronchodilating effects of salmeterol, theophylline and their combination in patients with moderate to severe asthma.

Ten patients with moderate to severe asthma (mean FEV1GSD: 57.3G5.8% of predicted) participated in this 4-day single-blind, placebocontrolled, crossover study, aimed to comparatively evaluate the bronchodilating effects of a single dose of inhaled salmeterol (50 mg) and oral slow-release theophylline (Theo-Dur, 600 mg tablets), used either alone or in combination. In particular, FEV1 was recorded at baseline and 2, 4, 6, 8, 10, and 12 h after drug administration; at the same times, with the exception of the 12th h, theophylline plasma concentrations were also measured. When compared to theophylline, bronchodilation induced by salmeterol was characterized by an earlier onset, a greater magnitude, and a longer duration. Given in combination with salmeterol, theophylline elicited a further slight increase in airway calibre with respect to the bronchodilator action of the b2-agonist alone, with FEV1 changes which resulted to be statistically significant at the 4th, 6th and 8th h after administration (p!0.05, p!0.03 and p!0.05, respectively). At the 4th h theophylline reached serum levels included within the therapeutic range, which were persistently maintained at least until the the 10th h. Therefore, our findings suggest that inhaled salmeterol and oral slow-release theophylline, the latter acting within the range of therapeutic plasma concentrations, exert additive bronchodilating effects in asthmatic patients with moderate to severe airflow limitation

Bouncing light beams and the Hamiltonian analogy

In this work we use the unusual behaviour of a light beam in a diffusion cell as an experimental introduction for university students of physics and engineering to the optical - mechanical analogy. We have found that the lecture demonstration is a key element in the development of the presentation and subsequent use of the analogy