Background and Purpose. Intervertebral disc (IVD) degeneration is a prominent cause of low back pain. IVD cells expressing angiopoietin-1 receptor Tie2 represent a progenitor cell population which decreases with progression of IVD degeneration. Homing of mesenchymal stem cells (MSCs) is a physiological mechanism aiming to enhance the regenerative capacity of the IVD. The purpose of this study was to assess the effect of MSC homing on the Tie2 positive IVD progenitor cell population, the IVD cell viability, and the proliferative phenotype of the IVD cells. Methods and Results. Human MSCs were isolated from bone marrow aspirates and labelled with fluorescent dye. Whole IVDs with endplates were harvested from bovine tails; MSCs were placed on the endplates. Human traumatic, degenerative and healthy IVD tissues were obtained from patients and organ donors. MSCs were added onto tissue samples. After 5 days, IVD cells were isolated. Percentages of Tie2 positive, DAPI positive (dead) and Ki-67 positive (proliferative) IVD cells were determined. MSC homing or co-culture significantly increased the proportion of Tie2 positive progenitor IVD cells in bovine and 7/10 human IVDs, decreased the fraction of dead IVD cells in bovine and 7/10 human IVDs, and induced a proliferative phenotype in bovine and 5/6 human IVDs. Conclusion. Stimulation of bovine and human IVDs by MSC homing resulted in an enhanced population of Tie2 positive IVD progenitor cells, induced a proliferative response and reduced IVD cell death. Hence, the interaction with recruited MSCs may contribute to an improved survival of IVD cells, helping to reverse or slow down an ongoing degenerative process. Conflicts of interest: The authors declare no conflicts of interest. Sources of funding: AO Foundation and AOSpine International

Introduction. Low back pain is the leading cause of musculoskeletal disease and the biggest cause of morbidity worldwide. Approximately 40% of these are cases are caused by disease of the intervertebral discs (IVDs): the shock absorbing, flexible material located between the bones (vertebrae) along the length of the spine. In severe cases, the spine becomes unstable and it becomes necessary to immobilise or fix the joint in position using a lumbar cage spacer between in the IVD and metal pins with supporting plates in the vertebrae. This is a complex, expensive, major surgery and it is associated with complications, such as spinal fusion failure and inappropriate implant position. These complications have a dramatic impact on the quality of life of the affected patients and the burden to society and the healthcare system is exacerbated. Methods and Results. We present an in vitro study looking at the effect of our Bgel hydrogel on mesenchymal stem cells (MSCs) and their bone forming capacity within lumbar cages: devices used to space the bones apart in the fusion operation, as a mechanism to improve fixation and intra cage bone formation. MSCs were isolated from human hip joint, expanded, seeded within Bgel, cast into well inserts or lumbar cages and cultured for 4 weeks. Using 3D X-ray imaging micro computed tomography (μCT) scans we show that the MSC in the presence Bgel begin to mineralise within the lumbar cages. Histology is currently ongoing and will be presented at the meeting. Conclusion. This study shows the potential to improve current spinal fusion practices with the potential to reduce complications. Conflicts of interest: CS and CLM are named inventors on the patent for NPgel/BGel. Funded by the Medical Research Council and Versus Arthritis UK: SNiPER

Background. Currently, there is a focus on the development of cell based therapies to treat intervertebral disc (IVD) degeneration, particularly for regenerating/repairing the central region, the nucleus pulposus (NP). Recently, we demonstrated that GDF6 promotes NP-like differentiation in mesenchymal stem cells (MSCs). However, bone marrow- (BM-MSCs) and adipose- (Ad-MSCs) showed differential responses to GDF6, with Ad-MSCs adopting a more NP-like phenotype. Here, we investigated GDF6 signalling in BM-MSCs and Ad-MSCs, with the aim to improve future IVD stem cell therapies. Methods. GDF6 receptor expression in patient-matched BM-MSCs and Ad-MSCs (N=6) was profiled through western blot and immunocytochemistry (ICC). GDF6 signal transduction was investigated through stimulation with 100 ng ml. −1. GDF6 for defined time periods. Subsequently smad1/5/9 phosphorylation and alternative non-smad pathway activation (phospho-p38; phospho-Erk1/2) was analysed (western blot, ELISA). Their role in inducing NP-like gene expression in Ad-MSCs was examined through pathway specific inhibitors. Results. Western blot and ICC established that BMPR profiles differed between MSC populations; specifically, BMPR2 (a GDF6 receptor) expression, was significantly higher in Ad-MSCs (p<0.05). ELISA and western blot analysis showed that smad1/5/9 phosphorylation was significantly higher in Ad-MSCs following GDF6 stimulation (p<0.05). GDF6 stimulation also phosphorylated p38 and Erk1/2 pathways. Blocking of both smad and non-smad pathways resulted in variation of GDF6 induced NP-like gene expression. Conclusions. The upregulation of BMPR2 in Ad-MSCs and corresponding differences in smad1/5/9 and non-smad pathway phosphorylation in response to GDF6 indicates an enhanced discogenic potential in Ad-MSCs, suggesting they may be more suitable for GDF6 mediated cellular IVD regeneration. Conflicts of interest. No conflicts of interest. Sources of funding. We would like to acknowledge UKRMP Acellular Hub, MRC, NIHR Musculoskeletal BRU and The Rosetrees Trust for funding this research

Introduction. Current strategies to treat back pain address the symptoms but not the underlying cause. Here we are investigating a novel hydrogel material (NPgel) which can promote MSC differentiation to Nucleus pulposus cells. Current in vitro studies have only explored conditions that mimic the native disc microenvironment. Here, we aim to determine the stem cells regenerative capacity under conditions that mimic the degenerate environment seen during disc degeneration. Methods. hMSCs were encapsulated in NPgel and cultured for 4 weeks under hypoxia (5%) with ± calcium (2.5mM and 5.0mM CaCl. 2. ), IL-1β and TNFα either individually or in combination to mimic the degenerate microenvironment. Cell viability was assessed by Alamar blue assay. Histological and immunohistochemical analysis investigated altered matrix and matrix degrading enzyme expression. Results. Viability of hMSCs was maintained under all culture conditions. Matrix deposition of glycosaminoglycans were observed under all conditions, MMP13 expression was upregulated by calcium but not by pro-inflammatory cytokines IL-1β and TNFα. Conclusions. We are developing an in vitro modelling system which can be used to test novel therapies within a degenerate microenvironment. Interestingly, our preliminary findings suggest calcium is a major contributor to regulating MMP13 in this model system. Investigating the degenerate niche will identify targets for inhibition to provide the correct niche to promote regeneration of the IVD. No conflict of interest. Funding: BMRC, MERI Sheffield Hallam University, for joint funding the Daphne Jackson Trust fellowship

Purpose and background. A review of secondary healthcare provision for civilians suffering persistent pain and living in the British Forces Germany (BFG) community was carried out in order to better inform referral from primary care. This population consists mostly of British nationals each with differing linguistic skills and cultural backgrounds. Patients may be referred to Evangelisches Krankenhaus Bielefeld (EvKB) in Germany or to Guys and St Thomas' NHS Foundation Trust (GSTT) in the UK. It was considered important to identify potential language or cultural-related barriers to improve decision making when considering where best to refer for a pain management programme (PMP). Methods. Clinical visits undertaken at GSTT and EvKB involved observation of clinical activities, collection of documentation and informal staff discussions. Data were organised into common themes and categorised to provide information for written reflective accounts on each visit. Results. The PMP at EvKB is medical doctor-led, supported by integrated psychologists. English language skills of individual staff members appear varied. Patients stay in shared rooms on a medical ward environment. Group based pain education here is provided in German only. Access to the GSTT PMP requires competent English language skills. It is psychologist-led and delivered by an interdisciplinary team. Patients reside in individual living accommodation and attend group therapy sessions. Conclusion. To reduce risk of increasing anxiety, cultural differences related to language, medical hierarchy and privacy should be considered before referring non-German speakers with complex psychosocial needs to EvKB. Given the complexity of pain, non-native speakers may misunderstand translations of cultural nuances used in pain education. No conflicts of interest. Funding was received by the primary author from SSAFA Forces Help for dissertation tuition fees. This work formed part of a project submitted in partial fulfilment of the requirements for the degree of MSc Clinical Management of Pain at the University of Edinburgh

Objectives. This paper describes the outcomes obtained from a 12 hour group based multidisciplinary functional restoration programme for patients with persistent low back pain who presented with psychosocial obstacles to recovery. The programme was designed to address modifiable psychosocial obstacles to recovery over a four week period, reduce pain related disability, improve pain self-efficacy and reduce patients' reliance on analgesic medication. Design. A single group retrospective analysis. Participants. Data from 54 participants with non-specific low back pain (Male = 26. Female =28, mean age 43.7yrs) who attended a four week functional restoration programme between September 2012 and June 2013 were analysed. Results. There was a statistically significant improvement between Oswestry Disability Index and Pain Self Efficacy scores before and after the treatment intervention, and at 9 month follow-up (p<0.001). When only scores at the end of the treatment intervention and month 9 were compared there was no significant difference (p=0.184 for ODI, p=0.341 for PSEQ). Patients also self-reported reduced reliance on analgesic medication after the treatment intervention and at 9 month follow-up. Conclusion. The findings indicate that a group based multidisciplinary functional restoration programme for patients with persistent low back pain, which targets modifiable obstacles to recovery, can be effective in reducing disability, improving self-efficacy and reducing reliance on medication in both the short and medium term. This article has also been published online in Wiley Online Library (. wileyonlinelibrary.com. ) DOI: 10.1002/msc.1078 in Musculoskeletal Care Journal (2014) © 2014 John Wiley & Sons, Ltd. Conflicts of interest: No conflicts of interest. Sources of funding: No funding obtained

Aims

Non-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI.

Objectives

Pulsed electromagnetic field (PEMF) stimulation was evaluated after anterior cervical discectomy and fusion (ACDF) procedures in a randomized, controlled clinical study performed for United States Food and Drug Administration (FDA) approval. PEMF significantly increased fusion rates at six months, but 12-month fusion outcomes for subjects at elevated risk for pseudoarthrosis were not thoroughly reported. The objective of the current study was to evaluate the effect of PEMF treatment on subjects at increased risk for pseudoarthrosis after ACDF procedures.