Advertisement for orthosearch.org.uk
Results 1 - 20 of 64
Results per page:
The Bone & Joint Journal
Vol. 101-B, Issue 3 | Pages 246 - 252
1 Mar 2019
Iwata E Scarborough M Bowden G McNally M Tanaka Y Athanasou NA

Aims. The aim of this study was to determine the diagnostic utility of histological analysis in spinal biopsies for spondylodiscitis (SD). Patients and Methods. Clinical features, radiology, results of microbiology, histology, and laboratory investigations in 50 suspected SD patients were evaluated. In 29 patients, the final (i.e. treatment-based) diagnosis was pyogenic SD; in seven patients, the final diagnosis was mycobacterial SD. In pyogenic SD, the neutrophil polymorph (NP) infiltrate was scored semi-quantitatively by determining the mean number of NPs per (×400) high-power field (HPF). Results. Of the 29 pyogenic SD patients, 17 had positive microbiology and 21 positive histology (i.e. one or more NPs per HPF on average). All non-SD patients showed less than one NP per HPF. The presence of one or more NPs per HPF had a diagnostic sensitivity of 72.4%, specificity 100%, accuracy 100%, positive predictive value (PPV) 81.0%, and negative predictive value (NPV) 61.9%. Sensitivity, specificity, and accuracy were greater using the criterion of positive histology and/or microbiology than positive histology or microbiology alone. Granulomas were identified histologically in seven mycobacterial SD patients, and positive microbiology was detected in four. Conclusion. The diagnosis of pyogenic SD was more often confirmed by positive histology (one or more NPs per HPF on average) than by microbiology, although diagnostic sensitivity was greater when both histology and microbiology were positive. Cite this article: Bone Joint J 2019;101-B:246–252


The Bone & Joint Journal
Vol. 104-B, Issue 1 | Pages 120 - 126
1 Jan 2022
Kafle G Garg B Mehta N Sharma R Singh U Kandasamy D Das P Chowdhury B

Aims. The aims of this study were to determine the diagnostic yield of image-guided biopsy in providing a final diagnosis in patients with suspected infectious spondylodiscitis, to report the diagnostic accuracy of various microbiological tests and histological examinations in these patients, and to report the epidemiology of infectious spondylodiscitis from a country where tuberculosis (TB) is endemic, including the incidence of drug-resistant TB. Methods. A total of 284 patients with clinically and radiologically suspected infectious spondylodiscitis were prospectively recruited into the study. Image-guided biopsy of the vertebral lesion was performed and specimens were sent for various microbiological tests and histological examinations. The final diagnosis was determined using a composite reference standard based on clinical, radiological, serological, microbiological, and histological findings. The overall diagnostic yield of the biopsy, and that for each test, was calculated in light of the final diagnosis. Results. The final diagnosis was tuberculous spondylodiscitis in 250 patients (88%) and pyogenic spondylodiscitis in 22 (7.8%). Six (2.1%) had a noninfectious condition-mimicking infectious spondylodiscitis, and six (2.1%) had no definite diagnosis and improved without specific treatment. The diagnosis was made by image-guided biopsy in 152 patients (56%) with infectious spondylodiscitis. Biopsy was contributory in identifying 132/250 patients (53%) with tuberculous spondylodiscitis, and 20/22 patients (91%) with pyogenic spondylodiscitis. Histological examination was the most sensitive diagnostic modality, followed by Xpert MTB/RIF assay. Conclusion. Image-guided biopsy has a reasonably high diagnostic yield in patients with suspected infectious spondylodiscitis. A combination of histological examination, Xpert MTB/RIF assay, bacterial culture, and sensitivity provides high diagnostic accuracy in a country in which TB is endemic. Cite this article: Bone Joint J 2022;104-B(1):120–126


The Bone & Joint Journal
Vol. 105-B, Issue 2 | Pages 172 - 179
1 Feb 2023
Shimizu T Kato S Demura S Shinmura K Yokogawa N Kurokawa Y Yoshioka K Murakami H Kawahara N Tsuchiya H

Aims. The aim of this study was to investigate the incidence and characteristics of instrumentation failure (IF) after total en bloc spondylectomy (TES), and to analyze risk factors for IF. Methods. The medical records from 136 patients (65 male, 71 female) with a mean age of 52.7 years (14 to 80) who underwent TES were retrospectively reviewed. The mean follow-up period was 101 months (36 to 232). Analyzed factors included incidence of IF, age, sex, BMI, history of chemotherapy or radiotherapy, tumour histology (primary or metastasis; benign or malignant), surgical approach (posterior or combined), tumour location (thoracic or lumbar; junctional or non-junctional), number of resected vertebrae (single or multilevel), anterior resection line (disc-to-disc or intravertebra), type of bone graft (autograft or frozen autograft), cage subsidence (CS), and local alignment (LA). A survival analysis of the instrumentation was performed, and relationships between IF and other factors were investigated using the Cox regression model. Results. A total of 44 patients (32.4%) developed IF at a median of 31 months (interquartile range 23 to 74) following TES. Most IFs were rod fractures preceded by a mean CS of 6.1 mm (2 to 18) and LA kyphotic enhancement of 10.8° (-1 to 36). IF-free survival rates were 75.8% at five years and 56.9% at ten years. The interval from TES to IF peaked at two to three years postoperatively and continued to occur over a period of time thereafter; the early IF-developing group had greater CS at one month postoperatively (CS1M) and more lumbar TES. CS1M ≥ 3 mm and sole use of frozen autografts were identified as independent risk factors for IF. Conclusion. IF is a common complication following TES. We have demonstrated that robust spinal reconstruction preventing CS, and high-quality bone grafting are necessary for successful reconstruction. Cite this article: Bone Joint J 2023;105-B(2):172–179


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_15 | Pages 20 - 20
7 Aug 2024
Snuggs J Ciccione C Vernengo A Tryfonidou M Grad S Vadala G Maitre CL
Full Access

Background. Chronic low back pain is strongly linked to degeneration of the intervertebral disc (IVD), which currently lacks any targeted treatments. This study explores NPgel, a biomaterial combined with notochordal cells (NC), developmental precursor cells, as a potential solution. NCs, known for anti-catabolic effects on IVD cells, present a promising avenue for regenerating damaged IVD tissue. Methods. Bovine IVDs underwent enzymatic degeneration before NPgel (+/- NC) injection. Degenerated bovine IVDs were cultured under biomechanical loading for 21 days. Histology and immunohistochemistry assessed NC survival, phenotype, and matrix production. Within an in vivo sheep pilot study, NPgel (+/- NC) was injected into degenerated IVDs, blood was taken, and immune cell activation was monitored via flow cytometry over three months post-injection. Results. Within the ex vivo model, IVDs injected with NPgel (+/- NC) exhibited increased matrix expression and deposition. Viable NCs were detected post-culture, indicating survival and matrix production. In the in vivo model, NPgel injection into sheep IVDs did not significantly increase activation of immune cells compared to controls, suggesting no systemic inflammatory effects. Conclusion. NPgel, combined with NCs, shows promise for IVD regeneration. Ex vivo findings indicate NPgel supports NC survival and matrix production. Moreover, in vivo results demonstrate the absence of systemic immunogenic responses post-NPgel injection. This suggests NPgel's potential as a carrier for NCs in IVD regeneration therapy. These findings underscore NPgel's candidacy for further investigation in addressing chronic low back pain associated with IVD degeneration. Subsequent research, including long-term efficacy and safety evaluations, is imperative for clinical translation. Conflicts of interest. There are no conflicts of interest. Sources of funding. iPSpine, grant # 825925, Horizon 2020


Background. Magnetic resonance imaging (MRI) algorithm identifies end stage severely degenerated disc as ‘black’, and a moderately degenerate to non-degenerated disc as ‘white’. MRI is based on signal intensity changes that identifies loss of proteoglycans, water, and general radial bulging but lacks association with microscopic features such as fissure, endplate damage, persistent inflammatory catabolism that facilitates proteoglycan loss leading to ultimate collapse of annulus with neo-innervation and vascularization, as an indicator of pain. Thus, we propose a novel machine learning based imaging tool that combines quantifiable microscopic histopathological features with macroscopic signal intensities changes for hybrid assessment of disc degeneration. Methods. 100-disc tissue were collected from patients undergoing surgeries and cadaveric controls, age range of 35–75 years. MRI Pfirrmann grades were collected in each case, and each disc specimen were processed to identify the 1) region of interest 2) analytical imaging vector 3) data assimilation, grading and scoring pattern 4) identification of machine learning algorithm 5) predictive learning parameters to form an interface between hardware and software operating system. Results. Kernel algorithm defines non-linear data in xy histogram. X,Y values are scored histological spatial variables that signifies loss of proteoglycans, blood vessels ingrowth, and occurrence of tears or fissures in the inner and outer annulus regions mapped with the dampening and graded series of signal intensity changes. Conclusion. To our knowledge this study is the first to propose a machine learning method between microscopic spatial tissue changes and macroscopic signal intensity grades in the intervertebral disc. No conflict of interest declared.  . Sources of Funding. ICMR/5/4-5/3/42/Neuro/2022-NCD-1, Dr TMA PAI SMU/ 131/ REG/ TMA PURK/ 164/2020. A part of the above study was presented as an oral paper at the International Society for the Study of Lumbar Spine (ISSLS) meeting held on 1–5. th. May 2023, Melbourne, Australia


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_9 | Pages 22 - 22
1 Oct 2022
Owen D Snuggs J Michael A Cole A Chiverton N Breakwell L Sammon C Le Maitre C
Full Access

Background. Current clinical treatment for spinal instability requires invasive spinal fusion with cages and screw instrumentation. We previously reported a novel injectable hydrogel (Bgel), which supports the delivery and differentiation of mesenchymal stem cells (MSCs) to bone forming cells and supports bone formation in vivo. Here, we investigated whether this system could be utilised to induce bone formation within intervertebral disc tissue as a potential injectable spinal fusion approach. Methodology. Bovine and Human Nucleus pulpous tissue explants were injected with Bgel with and without MSCs. Tissue samples were cultured under hypoxia (5%) in standard culture media for 4 weeks. Cell viability, histological assessment of matrix deposition, calcium formation, and cell phenotype analysis using immunohistochemistry for NP matrix and bone markers. Results. Following injection of B-gel into tissue explants following culture for 4 weeks, cells were visualized within the regions of the B-gel. Demonstrating that native cells were able to migrate into regions of B-gel. Increased collagen deposition was seen in tissue explants injected with Bgel, with increased collagen type I and X but decreased collagen type II staining in explants injected with Bgel. Tissue explants, in the absence of Bgel, showed limited calcium deposition, which was increased in B-gel injected explants. Furthermore, disc cells increased expression of bone markers (alkaline phosphatase & osteocalcin), but decreased NP matrix (Aggrecan and Collagen type II) following Bgel injection. Conclusion. This system could have potential to support spinal fusion via direct injection into the disc. Conflict of interest: C Le Maitre & C Sammon are inventors on the hydrogel discussed. Funding: This work was funded by GrowMed Tech Proof of Concept funding


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_9 | Pages 2 - 2
1 Oct 2022
Cherif H Li L Snuggs J Sammon C Beckman L Haglund L Le Maitre C
Full Access

Background. We have previously reported an injectable hydrogel (NPgel), which could deliver patients own stem cells, via small bore needles, decreasing damage to the annulus fibrosus. NPgel drives differentiation to NP cells and can inhibit the degenerate niche. However, clinical success of NPgel is dependent on the capacity to inject NPgel into naturally degenerate human discs, restore mechanical function to the IVD, prevent extrusion during loading and induce regeneration. This study assessed injectability of NPgel into human IVD, influence on mechanical properties, regeneration ability in an ex vivo culture system and retention under failure testing. Methodology. Cadaveric human discs were used to calculate disc height and to determine Youngs Modulus during simulated walking pre and post injection of NPgel, extrusion testing performed. Whole human IVDs were injected with NPgel +/− human BMPCs and maintained in culture under physiological loading regime for 4 weeks. Pre and post culture MRI imaging and in line biomechanical characteristics determined. Histology and immunochemistry performed for anabolic and catabolic factors. Results. NPgel injection significantly increased disc height and Youngs modulus with no extrusion observed during failure testing. T1ρ intensity was increased during culture in those injected with NPgel +/− cells compared to non-injected discs, and biomechanical restoration. Histological analysis has demonstrated excellent tissue attachment to the injected gel, and cellular migration into acellular gel systems. With increased matrix production and decreased catabolic factor expression. Conclusion. These results provide essential proof of concept data supporting the use of NPgel as an injectable therapy for disc regeneration. Conflict of interest: C Le Maitre & C Sammon are inventors on the hydrogel discussed. Funding: This work was funded by MRC and Versus Arthritis


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_8 | Pages 7 - 7
1 Aug 2022
Mathieu H Amani H Patten SA Parent S Aragon J Barchi S Joncas J Child A Moldovan F
Full Access

The aim of this study is to clarify the implication of ciliary pathway on the onset of the spinal curvature that occurs in Adolescent Idiopathic Scoliosis (AIS) patients through functional studies of two genes: POC5 and TTLL11. Since the genetic implication for AIS is accepted, many association and candidate gene analysis revealed the implication of ciliary genes. The characterisation of these two proteins was assessed by qPCR, WB and immunofluorescence in vitro using control cells and cells derived from AIS patients. The impact of genetic modification of these genes on the functionality of the proteins in vitro and in vivo was analysed in zebrafish model created by CRISPR/Cas9 using microCT and histologic analysis. Our study revealed that mutant cells, for both gene, were less ciliated and the primary cilia was significantly shorter compared to control cells. We also observed a default in cilia glutamylation by immunofluorescence and Western Blot. Moreover, we observed in both zebrafish model, a 3D spine curvature similar to the spinal deformation in AIS. Interestingly, our preliminary results of immunohistology showed a retinal defect, especially at the cone cell layer level. This study strongly supports the implication of the ciliary pathway in the onset of AIS and this is the first time that a mechanism is described for AIS. Indeed, we show that shorter cilia could be less sensitive to environmental factors due to lower glutamylation and result in altered signalling pathway. Identifying the biological mechanism involved is crucial for elucidating AIS pathogenesis


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_11 | Pages 17 - 17
1 Sep 2021
Sivasubramaniam V Fragkakis A Ho P Fenner C Ajayi B Crocker MJ Minhas P Lupu C Bishop T Bernard J Lui DF
Full Access

Introduction. Treatment of spinal metastatic disease has evolved with the advent of advanced interventional, surgical and radiation techniques. Spinal Oligometastatic disease is a low volume disease state where en bloc resection of the tumour, based on oncological principles, can achieve maximum local control (MLC). Hybrid therapy incorporating Separation surgery (>2mm clearance of the thecal sac) and Stereotactic Ablative Radiotherapy (SABR) offer an alternative approach to achieving MLC. Hybrid therapy is also a viable option in patients eligible for SBRT who have failed conventional radiation therapy. En-bloc surgery may be a suitable option for those patients who are ineligible for or have failed SBRT. A multidisciplinary approach is particularly important in the decision-making process for these patients. Metal free instrumentation is aiding the optimization of these surgeries. The authors present a supra-regional centre's experience in managing spinal oligometastases. Methods. Retrospective review of oligometastatic spinal disease at a supra-regional centre between 2017 and 2021. Demographics, operative course, complications and Instrument type are examined. Results. Demographics: 24 patients with mean age 53.8y (range 12–77), 44% (40y–59y), 40% (60y–69y); 51% Male. Histology: Breast, Renal and Sarcoma accounted for 16.7% each; Thyroid, Prostate and Chordoma accounted for 8.3% each. Primary disease 7%, Synchronous 15%, Metachronous 78%. Instrumentation: Carbon-fibre (85%), TiAl (11%), Non-Instrumented (3%). Separation Surgery (70%), En-bloc resection/Tomita surgery (30%); SABR/Proton Beam Planned: 70%. Average length of hospital stays 19.1 days; twenty patients required intensive care admission for an average 2.7 days. 30 Day Mortality 8.3% (n=2: COVID-19 during admission and ventriculitis post discharge), 1y Mortality – 16.7%, 3y Mortality – 25%; Synchronous Mortality 75% (n=3) at 3 years. 30 Day infection rate 3%; 1y infection rate 7%. 1 Non-instrumented case developed proximal junctional failure post proton beam therapy and required a vascularised fibular strut graft. 2-year Revision for Local Recurrence 5% (Revision at 23 months). Conclusion. There are very few case series of oligometastatic spinal disease due to the relatively new concept of adjuvant SABR and its limited availability. Solid tumours pre-dominated the histology in our series with metachronous disease being the most commonly operated disease state. 92% of cases were eligible for SABR. The majority (85%) of cases were performed with Carbon-fibre instrumentation and has been shown to be safe with no mechanical failures in this series. Infection rates are in keeping with patients requiring radical radiotherapy with 3% early and 7% late. 30-day mortality was 8.3%, 1y=16.7% and 25% at last follow up. Mortality, as expected, is highest within the synchronous disease group and should be operated on sparingly. With the current management strategy, there was no local recurrence at 1 year and excellent local recurrence rate at 2 years (5%). Although radical en bloc surgery carries significant morbidity, it should be considered in selective cases to achieve MLC. All Oligometastatic cases deserve extra consideration and specialist MDT as not all are suitable for SABR. Multimodal Hybrid therapy, incorporating less invasive surgical techniques and SABR, represents a paradigm shift in achieving MLC in oligometastatic spinal disease


The Bone & Joint Journal
Vol. 102-B, Issue 10 | Pages 1375 - 1383
3 Oct 2020
Zhang T Sze KY Peng ZW Cheung KMC Lui YF Wong YW Kwan KYH Cheung JPY

Aims. To investigate metallosis in patients with magnetically controlled growing rods (MCGRs) and characterize the metal particle profile of the tissues surrounding the rod. Methods. This was a prospective observational study of patients with early onset scoliosis (EOS) treated with MCGRs and undergoing rod exchange who were consecutively recruited between February 2019 and January 2020. Ten patients were recruited (mean age 12 years (SD 1.3); 2 M:8 F). The configurations of the MCGR were studied to reveal the distraction mechanisms, with crucial rod parts being the distractable piston rod and the magnetically driven rotor inside the barrel of the MCGR. Metal-on-metal contact in the form of ring-like wear marks on the piston was found on the distracted portion of the piston immediately outside the barrel opening (BO) through which the piston rod distracts. Biopsies of paraspinal muscles and control tissue samples were taken over and away from the wear marks, respectively. Spectral analyses of the rod alloy and biopsies were performed to reveal the metal constituents and concentrations. Histological analyses of the biopsies were performed with haematoxylin and eosin staining. Results. Titanium (Ti), vanadium (V), and neodymium (Nd) concentrations in the biopsies taken near the wear marks were found to be significantly higher than those in the control tissue samples. Significantly increased Nd concentrations were also found in the tissues near the barrel of the MCGR. Chronic inflammation was revealed by the histological studies with fibrosis and macrophage infiltration. Black particles were present within the macrophages in the fibrotic tissues. Conclusion. Ti and V were generated mainly at the BO due to metal-on-metal contact, whereas the Nd from the rotor of the MCGR is likely released from the BO during distraction sessions. Phagocytotic immune cells with black particles inside raise concern regarding the long-term implications of metallosis. Cite this article: Bone Joint J 2020;102-B(10):1375–1383


Bone & Joint Open
Vol. 4, Issue 11 | Pages 832 - 838
3 Nov 2023
Pichler L Li Z Khakzad T Perka C Pumberger M Schömig F

Aims

Implant-related postoperative spondylodiscitis (IPOS) is a severe complication in spine surgery and is associated with high morbidity and mortality. With growing knowledge in the field of periprosthetic joint infection (PJI), equivalent investigations towards the management of implant-related infections of the spine are indispensable. To our knowledge, this study provides the largest description of cases of IPOS to date.

Methods

Patients treated for IPOS from January 2006 to December 2020 were included. Patient demographics, parameters upon admission and discharge, radiological imaging, and microbiological results were retrieved from medical records. CT and MRI were analyzed for epidural, paravertebral, and intervertebral abscess formation, vertebral destruction, and endplate involvement. Pathogens were identified by CT-guided or intraoperative biopsy, intraoperative tissue sampling, or implant sonication.


The Bone & Joint Journal
Vol. 105-B, Issue 5 | Pages 575 - 582
1 May 2023
Kato S Demura S Yokogawa N Shimizu T Kobayashi M Yamada Y Murakami H Tsuchiya H

Aims

Patients with differentiated thyroid carcinomas (DTCs) have a favourable long-term survival. Spinal metastases (SMs) cause a decline in performance status (PS), directly affecting mortality and indirectly preventing the use of systemic therapies. Metastasectomy is indicated, if feasible, as it yields the best local tumour control. Our study aimed to examine the long-term clinical outcomes of metastasectomy for SMs of thyroid carcinomas.

Methods

We collected data on 22 patients with DTC (16 follicular and six papillary carcinomas) and one patient with medullary carcinoma who underwent complete surgical resection of SMs at our institution between July 1992 and July 2017, with a minimum postoperative follow-up of five years. The cancer-specific survival (CSS) from the first spinal metastasectomy to death or the last follow-up was determined using Kaplan-Meier analysis. Potential factors associated with survival were evaluated using the log-rank test. We analyzed the clinical parameters and outcome data, including pre- and postoperative disability (Eastern Cooperative Oncology Group PS 3), lung and non-spinal bone metastases, and history of radioiodine and kinase inhibitor therapies.


Bone & Joint Open
Vol. 5, Issue 10 | Pages 886 - 893
15 Oct 2024
Zhang C Li Y Wang G Sun J

Aims

A variety of surgical methods and strategies have been demonstrated for Andersson lesion (AL) therapy. In 2011, we proposed and identified the feasibility of stabilizing the spine without curettaging the vertebral or discovertebral lesion to cure non-kyphotic AL. Additionally, due to the excellent reunion ability of ankylosing spondylitis, we further came up with minimally invasive spinal surgery (MIS) to avoid the need for both bone graft and lesion curettage in AL surgery. However, there is a paucity of research into the comparison between open spinal fusion (OSF) and early MIS in the treatment of AL. The purpose of this study was to investigate and compare the clinical outcomes and radiological evaluation of our early MIS approach and OSF for AL.

Methods

A total of 39 patients diagnosed with AL who underwent surgery from January 2004 to December 2022 were retrospectively screened for eligibility. Patients with AL were divided into an MIS group and an OSF group. The primary outcomes were union of the lesion on radiograph and CT, as well as the visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores immediately after surgery, and at the follow-up (mean 29 months (standard error (SE) 9)). The secondary outcomes were total blood loss during surgery, operating time, and improvement in the radiological parameters: global and local kyphosis, sagittal vertical axis, sagittal alignment, and chin-brow vertical angle immediately after surgery and at the follow-up.


Bone & Joint Research
Vol. 12, Issue 9 | Pages 522 - 535
4 Sep 2023
Zhang G Li L Luo Z Zhang C Wang Y Kang X

Aims

This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD).

Methods

The gene expression profile of GSE23130 was downloaded from the Gene Expression Omnibus (GEO) database. Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases, and we used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the functions and pathways of EP-DEGs. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and identify hub EP-DEGs. NetworkAnalyst was used to analyze transcription factors (TFs) and microRNAs (miRNAs) that regulate hub EP-DEGs. A search of the Drug Signatures Database (DSigDB) for hub EP-DEGs revealed multiple drug molecules and drug-target interactions.


Bone & Joint Research
Vol. 12, Issue 1 | Pages 80 - 90
20 Jan 2023
Xu J Si H Zeng Y Wu Y Zhang S Liu Y Li M Shen B

Aims

Degenerative cervical spondylosis (DCS) is a common musculoskeletal disease that encompasses a wide range of progressive degenerative changes and affects all components of the cervical spine. DCS imposes very large social and economic burdens. However, its genetic basis remains elusive.

Methods

Predicted whole-blood and skeletal muscle gene expression and genome-wide association study (GWAS) data from a DCS database were integrated, and functional summary-based imputation (FUSION) software was used on the integrated data. A transcriptome-wide association study (TWAS) was conducted using FUSION software to assess the association between predicted gene expression and DCS risk. The TWAS-identified genes were verified via comparison with differentially expressed genes (DEGs) in DCS RNA expression profiles in the Gene Expression Omnibus (GEO) (Accession Number: GSE153761). The Functional Mapping and Annotation (FUMA) tool for genome-wide association studies and Meta tools were used for gene functional enrichment and annotation analysis.


Bone & Joint Research
Vol. 12, Issue 3 | Pages 189 - 198
7 Mar 2023
Ruiz-Fernández C Ait Eldjoudi D González-Rodríguez M Cordero Barreal A Farrag Y García-Caballero L Lago F Mobasheri A Sakai D Pino J Gualillo O

Aims

CRP is an acute-phase protein that is used as a biomarker to follow severity and progression in infectious and inflammatory diseases. Its pathophysiological mechanisms of action are still poorly defined. CRP in its pentameric form exhibits weak anti-inflammatory activity. The monomeric isoform (mCRP) exerts potent proinflammatory properties in chondrocytes, endothelial cells, and leucocytes. No data exist regarding mCRP effects in human intervertebral disc (IVD) cells. This work aimed to verify the pathophysiological relevance of mCRP in the aetiology and/or progression of IVD degeneration.

Methods

We investigated the effects of mCRP and the signalling pathways that are involved in cultured human primary annulus fibrosus (AF) cells and in the human nucleus pulposus (NP) immortalized cell line HNPSV-1. We determined messenger RNA (mRNA) and protein levels of relevant factors involved in inflammatory responses, by quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. We also studied the presence of mCRP in human AF and NP tissues by immunohistochemistry.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_2 | Pages 6 - 6
1 Feb 2018
Richardson S Hodgkinson T White L Shakesheff K Hoyland J
Full Access

Background. Stem cell therapy has been suggested as a potential regenerative strategy to treat IVD degeneration and GDF6 has been shown to differentiate adipose-derived stem cells (ASCs) into an NP-like phenotype. However, for clinical translation, a delivery system is required to ensure controlled and sustained GDF6 release. This study aimed to investigate the encapsulation of GDF6 inside novel microparticles (MPs) to control delivery and assess the effect of the released GDF6 on NP-like differentiation of human ASCs. Methods. GDF6 release from PLGA-PEG-PLGA MPs over 14 days was determined using BCA and ELISA. The effect of MP loading density on collagen gel formation was assessed through SEM and histological staining. ASCs were cultured in collagen hydrogels for 14 days with GDF6 delivered exogenously or via microspheres. ASC differentiation was assessed by qPCR for NP markers, glycosaminoglycan production (DMMB) and immunohistochemistry. Results. GDF6 release from MPs was controlled over 14 days equivalently to exogenous addition. SEM and histology confirmed that MPs were distributed throughout gels and that gel formation was not disrupted. In 3D cultures, GDF6 release from microspheres elicited equivalent ASC differentiation and NP-like matrix formation compared to exogenous delivery in media, indicating activity was not affected by MP encapsulation. Conclusions. This study demonstrates the effective encapsulation and controlled delivery of GDF6, which was able to maintain its activity and induce ASC differentiation into an NP-like phenotype and production of an NP-like ECM. Delivery of GDF6 microspheres in combination with ASCs is a promising strategy for IVD regeneration and treatment of back pain. 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


Bone & Joint Open
Vol. 3, Issue 5 | Pages 348 - 358
1 May 2022
Stokes S Drozda M Lee C

This review provides a concise outline of the advances made in the care of patients and to the quality of life after a traumatic spinal cord injury (SCI) over the last century. Despite these improvements reversal of the neurological injury is not yet possible. Instead, current treatment is limited to providing symptomatic relief, avoiding secondary insults and preventing additional sequelae. However, with an ever-advancing technology and deeper understanding of the damaged spinal cord, this appears increasingly conceivable. A brief synopsis of the most prominent challenges facing both clinicians and research scientists in developing functional treatments for a progressively complex injury are presented. Moreover, the multiple mechanisms by which damage propagates many months after the original injury requires a multifaceted approach to ameliorate the human spinal cord. We discuss potential methods to protect the spinal cord from damage, and to manipulate the inherent inhibition of the spinal cord to regeneration and repair. Although acute and chronic SCI share common final pathways resulting in cell death and neurological deficits, the underlying putative mechanisms of chronic SCI and the treatments are not covered in this review.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_10 | Pages 45 - 45
1 Oct 2019
Partridge S Snugg J Michael A Cole A Chiverton N Sammon C Maitre C
Full Access

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


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_10 | Pages 17 - 17
1 Oct 2019
Snuggs J Thorpe A Partridge S Chiverton N Cole A Michael A Sammon C Le Maitre C
Full Access

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