Purpose of study and background. We have previously reported the development of injectable hydrogels for potential disc regeneration (NPgel) or bone formation which could be utilized in spinal fusion (Bgel). As there are multiple sources of mesenchymal stem cells (MSCs), this study investigated the incorporation of patient matched hMSCs derived from adipose tissue (AD) and bone marrow (BM) to determine their ability to differentiate within both hydrogel systems under different culture conditions. Methods and Results. Human fat pad and bone marrow derived MSCs were isolated from femoral heads of patients undergoing hip replacement surgery for osteoarthritis with informed consent. MSCs were encapsulated into either NPgel or Bgel and cultured for up to 6 weeks in 5% (NPgel) or 21% (Bgel) O. 2. Histology and immunohistochemistry was utilized to determine phenotype. Both fat and bone marrow derived MSCs, were able to differentiate into both cell lineages. NPgel culture conditions increased expression of matrix components such as collagen II and aggrecan and NP phenotypic markers FOXF1 and PAX1, whereas Bgel induced expression of collagen I and osteopontin, indicative of osteogenic differentiation. Conclusion. NPgel and Bgel were able to differentiate patient derived MSCs from different sources into both NP and osteogenic lineages, which may give rise to novel treatment strategies for IVD degeneration and spinal fusion, enabling choice for cell source according to patients' circumstances and needs. C Le Maitre and C Sammon hold a patent for the hydrogel described. Funded by MRC and Versus Arthritis

Background. Degeneration of the intervertebral disc (IVD) is a leading cause of lower back pain, and a significant clinical problem. Inflammation mediated by IL-1β and TNF-α drives IVD degeneration through promoting a phenotypic switch in the resident nucleus pulposus (NP) cells towards a more catabolic state, resulting in extracellular matrix degradation. Bone marrow mesenchymal stem cells (MSCs) produce bioactive factors that modulate local tissue microenvironments and their anti-inflammatory potential has been shown in numerous disease models. Thus MSCs offer a potential therapy for IVD degeneration. In a clinical setting, adipose-derived stem cells (ASCs) might represent an alternative and perhaps more appealing cell source. However, their anti-inflammatory properties remain poorly understood. Methods. Here we assess the anti-inflammatory properties of donor-matched human ASCs and MSCs using qPCR and western blotting. Results. We demonstrate that stimulating ASCs or MSCs with IL-1β and/or TNF-α elicits a strong anti-inflammatory response with increased expression of IL-1 receptor antagonist (IL-1Ra), cyclooxygenase-2 (COX-2) and the tissue protective protein tumour-necrosis factor stimulated gene-6 (TSG-6). ASCs produced significantly higher levels of IL-1Ra and TSG-6 than their matched MSCs at both gene and protein levels, indicating that ASCs are potentially a more potent anti-inflammatory cell type. This anti-inflammatory response was also observed upon co-culture with degenerate NP cells without exogenous cytokine. Signalling analyses suggested this difference between cell types might be mediated through differences in the activation of inflammation-associated transcription factors. Conclusion. These data indicate that the anti-inflammatory properties of ASCs may be useful in developing future therapies for IVD degeneration. No conflicts of interest. Sources of funding: EPSRC-MRC Centre for Doctoral Training in Regenerative Medicine (EP/L014904/1)

Aims

This study was performed to explore the effect of melatonin on pyroptosis in nucleus pulposus cells (NPCs) and the underlying mechanism of that effect.

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.

Objective. To evaluate functional and oncological outcomes following resection of sacral tumours and discuss the strategies for instrumentation. Introduction. Primary malignant tumours of the sacrum are rare, arising from bony or neural elements, or bone marrow in haematological malignancies. Management of such lesions is dictated by anatomy and the behaviour of tumours. Three key issues which arise are the adequacy of tumour resection, mechanical stabilisation and the need for colostomy. Stabilisation is often extensive and can be challenging. Methods. A retrospective review of the surgical management of primary malignant sacral tumours from 2004 - 2009. Results. The study included 46 patients (34 males, 12 females) with an average age of 49 (range 7 – 82). Median duration of symptoms before presentation was 26 months. 25 patients (54%) underwent surgical resection. 8 underwent instrumented stabilisations with fibula strut graft vs. 17 uninstrumented. Mechanical failure of stabilisation was noted in 75% over the follow up period but only one required revision surgery. Colostomy was performed in 10 patients (40%). Mean follow post-operatively was 19.0 months. Wound healing problems were present in 5/25 (20%). There was no difference in infection rates between definitive surgery with and without colostomy. There was one peri-operative death. Local recurrence occurred in 12%(3/25) of operated patients although follow-up period was noted to be short. Conclusions. Mechanical stabilisation for extensive lesions in the sacrum are particularly challenging in tumour surgery. Despite radiological failure in 7/8 instrumented stabilisations, patients were relatively asymptomatic and only 1/8 required revision stabilisation surgery. Ethics approval:. None: Audit. Interest Statement: None

To evaluate functional and oncological outcomes following resection of primary malignant bone tumours. Primary malignant tumours of the sacrum are rare, arising from bony or neural elements, or bone marrow in haematological malignancies. Management of these lesions is dictated by anatomical considerations and the behaviour of tumours. The three key issues which arise are the adequacy of tumour resection, mechanical stabilisation and the need for colostomy. A retrospective review of the surgical management of primary malignant sacral tumours from 2004 - 2009. The study included 46 patients (34 males, 12 females) with an average age of 49 (range 7 – 82). Median duration of symptoms before presentation was 26 months. 10 patients had inoperable tumours at presentation. 6 patients had chemotherapy. 2 patients opted for palliative radiotherapy. 1 patient was unfit for surgery. 25 patients (54%) underwent surgical resection. 8 underwent instrumented stabilisations with fibula strut graft vs. 17 uninstrumented. Colostomy was performed in 10 patients (40%). Mean follow post-operatively was 19.0 months. Wound healing problems were present in 5/25 (20%). There was no difference in infection rates between definitive surgery with and without colostomy. Mechanical failure of stabilisation was noted in 75%. There was one peri-operative death. Local recurrence occurred in 12%(3/25) of operated patients although follow-up period was noted to be short. Mechanical stabilisation for extensive lesions in the sacrum are particularly challenging in tumour surgery. Despite radiological failure in 7/8 instrumented stabilisations, patients were relatively asymptomatic and only 1/8 required revision stabilisation surgery. Ethics approval: None: Audit Interest Statement: None

Background. For bone grafting procedures, the use of autologous bone is considered the gold standard, as it is has a better healing capacity compared to other alternatives as allograft and synthetic bone substitutes. However, as there are several drawbacks related to autografting (infection, nerve- or vascular damage, chronic pain problems, abdominal herniation), there has been a targeted effort to improve the healing capacities of synthetic bone substitutes. Aim. To evaluate the performance of a carbonated osteoionductive hydroxyapatite (CHA) scaffold of clinical relevant size (Ø=15mm, H=50mm) in a sheep model of multi level posterolateral intertransverse lumbar spine fusion after activation with autologous bone marrow nuclear cells (BMNC) in a flow perfusion bioreactor. Method. Two groups were included in the study, autograft (n=6) and CHA scaffold (n=6) CHA. A paired design was used between and within the groups as lumbar posterolateral arthrodesis was performed in sheep on two levels (L2-L3, L5-L6) +/− BMNC, respectively. Before implantation, the CHA scaffold was cultured in a flow perfusion bioreactor system with BMNC for 21 days, and the autograft group was supplemented with isolated BMNC during the procedure. Micro tomography was used to evaluate fusion rate and the microarchitectural properties of the explants after an observation period of four months. Results. In the autograft group, the healing rate was 83.3% irrespective of the presence BMNC, and in the CHA group, 66.7% fused in the presence of BMNC, and 33.3% without. The microarchitectural data suggested the autograft group to be superior to the CHA scaffold regarding mechanical properties, however porosity decreased significantly (p=0.001) in the CHA scaffold group suggesting deposition of mineralized bone matrix. Conclusion. Based on the fusion rate and micro architectural properties, we consider the CHA scaffold fully capable of new bone formation, and that the presence of BMNC has a positive effect on the fusion rate in a challenging model of bone healing

The Royal Liverpool and Broadgreen University Hospital, Liverpool, UK. Plasmacytoma is the localised form of multiple myeloma, which can affect any part of the body including the axial skeleton (Kelly et al, 2006; Ampil et al, 1995). These myelomas/plasmacytomas arise from one malignant clone of cells, which secrete the same type of immunoglobulin. Where the clone of cells remains localised, it is known as plasmacytoma, but when there is spread of the malignancy to multiple bones and marrow, it is known as multiple myeloma (Boccadoro and Pileri, 1995). We present a case of solitary sacral bone plasmacytoma (SBP), in a seventy year old man which presented as low back pain, following a fall. He was neurologically intact, and had no sphincteric incontinence, but MRI revealed a large expansile lesion in S1, which caused severe spinal stenosis, involving the left L5 exiting foramen, with an irregular area of low signal posteriorly. Bone scan showed increased tracer uptake in L5 and a mixed hot/photopaenic appearance in the mid-sacral region indicating tumor involvement. Myeloma screen confirmed that the serum IgA was high, with positive kappa monoclonal band, positive Bence Jones Protein (BJP), normal IgM and IgG, and normal calcium profile. CT-guided biopsy revealed sheets of mature plasma cells, consistent with the diagnosis. Fine needle aspiration biopsy of an enlarged groin lymph node revealed neoplastic infiltration, consistent with myeloma. Skeletal survey and CT chest/abdomen/pelvis (CAP) were not contributory. The patient had six courses of radiotherapy and improved remarkably, and is being considered for chemotherapy as well as follow up in the out-patients' department

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.

The widespread use of MRI has revolutionised the diagnostic process for spinal disorders. A typical protocol for spinal MRI includes T1 and T2 weighted sequences in both axial and sagittal planes. While such an imaging protocol is appropriate to detect pathological processes in the vast majority of patients, a number of additional sequences and advanced techniques are emerging. The purpose of the article is to discuss both established techniques that are gaining popularity in the field of spinal imaging and to introduce some of the more novel ‘advanced’ MRI sequences with examples to highlight their potential uses.

Cite this article: Bone Joint J 2015;97-B:1683–92.

This short contribution aims to explain how intervertebral disc ‘degeneration’ differs from normal ageing, and to suggest how mechanical loading and constitutional factors interact to cause disc degeneration and prolapse. We suggest that disagreement on these matters in medico-legal practice often arises from a misunderstanding of the nature of ‘soft-tissue injuries’.

This article reviews the current knowledge of the intervertebral disc (IVD) and its association with low back pain (LBP). The normal IVD is a largely avascular and aneural structure with a high water content, its nutrients mainly diffusing through the end plates. IVD degeneration occurs when its cells die or become dysfunctional, notably in an acidic environment. In the process of degeneration, the IVD becomes dehydrated and vascularised, and there is an ingrowth of nerves. Although not universally the case, the altered physiology of the IVD is believed to precede or be associated with many clinical symptoms or conditions including low back and/or lower limb pain, paraesthesia, spinal stenosis and disc herniation.

New treatment options have been developed in recent years. These include biological therapies and novel surgical techniques (such as total disc replacement), although many of these are still in their experimental phase. Central to developing further methods of treatment is the need for effective ways in which to assess patients and measure their outcomes. However, significant difficulties remain and it is therefore an appropriate time to be further investigating the scientific basis of and treatment of LBP.

A number of causes have been advanced to explain the destructive discovertebral (Andersson) lesions that occur in ankylosing spondylitis, and various treatments have been proposed, depending on the presumed cause. The purpose of this study was to identify the causes of these lesions by defining their clinical and radiological characteristics.

We retrospectively reviewed 622 patients with ankylosing spondylitis. In all, 33 patients (5.3%) had these lesions, affecting 100 spinal segments. Inflammatory lesions were found in 91 segments of 24 patients (3.9%) and traumatic lesions in nine segments of nine patients (1.4%). The inflammatory lesions were associated with recent-onset disease; a low modified Stoke ankylosing spondylitis spine score (mSASSS) due to incomplete bony ankylosis between vertebral bodies; multiple lesions; inflammatory changes on MRI; reversal of the inflammatory changes and central bony ankylosis at follow-up; and a good response to anti-inflammatory drugs. Traumatic lesions were associated with prolonged disease duration; a high mSASSS due to complete bony ankylosis between vertebral bodies; a previous history of trauma; single lesions; nonunion of fractures of the posterior column; acute kyphoscoliotic deformity with the lesion at the apex; instability, and the need for operative treatment due to that instability.

It is essential to distinguish between inflammatory and traumatic Andersson lesions, as the former respond to medical treatment whereas the latter require surgery.