Background. Signalling by growth differentiation factor 6 (GDF6/BMP13) has been implicated in the development and maintenance of healthy NP cell phenotypes and GDF6 mutations are associated with defective vertebral segmentation in Klippel-Feil syndrome. GDF6 may thus represent a promising biologic for treatment of IVD degeneration. This study aimed to investigate the effect of GDF6 in human NP cells and critical signal transduction pathways involved. Methods. BMP receptor expression profile of non-degenerate and degenerate human NP cells was determined through western blot, immunofluorescence and qPCR. Phosphorylation statuses of Smad1/5/9 and non-canonical p38 MAPK and Erk1/2 were assessed in the presence/absence of pathway blockers. NP marker and matrix degrading enzyme gene expression was determined by qPCR following GDF6 stimulation. Glycosaminoglycan and collagen production were assessed through DMMB-assay and histochemical staining. Results. NP cells expressed all GDF6 receptor subunits, with receptor subunits BMPR-1A and BMPR2 displaying the highest expression and highest binding affinity. GDF6 stimulation significantly upregulated the expression of NP specific marker genes but had no significant effect on the expression of matrix degrading enzymes. Total glycosaminoglycan and collagen production was also significantly increased following GDF6 stimulation. Smad1/5/9, p38 MAPK and Erk1/2 pathways were phosphorylated following GDF6 stimulation and could be effectively blocked. Conclusions. These findings enhance our understanding of both the effects of GDF6 in NP cells and the mechanisms of GDF6 signal transduction that are critical to promote NP phenotype and cellular function. This knowledge is important for the effective use of GDF6 as a therapeutic molecule for treatment of IVD degeneration. 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

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.

Aims. To investigate the correlations among cytokines and regulatory T cells (T-regs) in ankylosing spondylitis (AS) patients, and their changes after anti-tumour necrosis factor-α (TNF-α) treatment. Methods. We included 72 AS patients with detailed medical records, disease activity score (Bath Ankylosing Spondylitis Disease Activity Index), functional index (Bath Ankylosing Spondylitis Functional Index), and laboratory data (interleukin (IL)-2, IL-4, IL-10, TNF-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, ESR, and CRP). Their peripheral blood mononuclear cells (PBMCs) were marked with anti-CD4, anti-CD25, and anti-FoxP3 antibodies, and triple positive T cells were gated by flow cytometry as T-regs. Their correlations were calculated and the changes after anti-TNF-α therapy were compared. Results. The frequency of T-regs in PBMCs was positively correlated to ESR and CRP in AS (r = 0.35 and 0.43; p = 0.032 and 0.027, respectively), and there was also a significant correlation between serum level of TNF-α and CRP (p = 0.041). The frequency of T-regs in PBMCs positively correlated to serum levels of TNF-α, IL-10, and TGF-β, while IL-2, IL-4, and IFN-γ showed opposite results. After anti-TNF-α treatment, there were significantly lower serum levels of TNF-α, IL-10, TGF-β, and frequency of T-regs in PBMCs among these AS patients (p = 0.026, 0.032, 0.029, and 0.037, respectively). Conclusion. In AS patients, proinflammatory cytokine may give positive feedback to induce more T-reg production and anti-inflammatory cytokine secretion to suppress this inflammatory status, and they can be reversed by anti-TNF-α therapy. However, the detailed interactions among T-regs and complex cytokine networks in autoinflammatory diseases still need more studies and further functional assay. Cite this article: Bone Joint Res 2023;12(2):133–137

AO Spine Reference Centre & Institute of Health & Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. Traumatic spinal cord injury (SCI) is a devastating condition with no curative therapy. Pro-inflammatory therapy has been suggested recently to try and reduce the inhibitory glial scar and promote neural regeneration and healing. The aim of this study is to investigate the potential of sustained delivery of angiogenic/pro-inflammatory growth factors to reduce the secondary degeneration after spinal cord injury. Adult male Wistar Kyoto rats (200-300g; 12-16weeks old) were subjected to cord hemisections via a T10 laminectomy. Animals were randomised to treatment or control groups after the spinal cord injury had been induced. Treatment consisted of implantation of a mini-osmotic pump capable of delivering 5 micrograms vascular endothelial growth factor (VEGF) and 5 micrograms platelet-derived growth factor (PDGF), via a catheter, to the site of the lesion, over 7 days(n=6). Control animals were subjected to either cord lesion only (n=6) or lesion plus mini-pump delivering PBS (phosphate-buffered saline) solution (n=6). Rats were sacrificed at one month and the spinal cords were harvested and examined by immunohistology, using anti-neurofilament-200 and anti-Glial Acidic Fibrillary Acidic Protein (GFAP) antibodies. RESULTS: Active treatment spinal cords showed a higher level with aboration of the axonal filament through the defect and more dense neurofilament-200 staining at the lesion site compared to both control groups. The treatment also showed the elevated presence of activated microglia in the lesion, whilst distal to the lesion the microglia and astrocytes retained an unreactive phenotype. Pro-inflammatory therapy in the rat spinal cord-injury model showed favourable histological findings after sustained delivery of PDGF and VEGF

Background. Intervertebral disc (IVD) degeneration is a major cause of low back pain (LBP). We have developed an injectable hydrogel (NPgel), which following injection into bovine IVD explants, integrates with IVD tissue and promotes disc cell differentiation of delivered mesenchymal stem cells (MSCs) without growth factors. Here, we investigated the injection of NPgel+MSCs into IVD explants under degenerate culture conditions. Methods and Results. The NPgel integrated with bovine and human degenerate Nucleus Pulposus (NP) tissue and hMSCs produced matrix components: aggrecan, collagen type II and chondroitin sulphate in standard and degenerate culture conditions. Significantly increased cellular immunopositivty for aggrecan was observed within native NP cells surrounding the site where NPgel+MSCs were injected (P≤0.05). In NP explants a significant decrease in catabolic factors were observed where NPgel+MSCs was injected in comparison to controls. Conclusions. In agreement with our previous findings NPgel was sufficient alone to induce NP cell differentiation of MSCs following injection into NP tissue explants. Here, we have shown that viability is maintained even in degenerate conditions. Injection of NPgel with MSCs increased aggrecan expression and reduced MMP3 and IL-1R1 expression by native NP cells. The NPgel with incorporated MSCs has the potential to regenerate the NP and provide mechanical support, whilst reducing the catabolic phenotype of degenerate NP cells, as a treatment strategy for IVD degeneration. No conflicts of interest. Sources of funding: Funded by ARUK and MRC

Introduction. Intervertebral disc degeneration (IVDD) associated with low back pain is a major contributor to global disability. Current treatments are poorly efficient in the long-term resulting in medical complications. Therefore, minimally invasive injectable therapies are required to repopulate damaged tissues and aid regeneration. Among injectable biomaterials, self-assembling peptide hydrogels (SAPHs) represent potential candidates as 3D cell carriers. Moreover, the advent of graphene-related materials has opened the route for the fabrication of graphene-containing hydrogel nanocomposites to direct cellular fate. Here, we incorporated graphene oxide (GO) within a SAPH to develop a biocompatible and injectable hydrogel to be used as cell carrier to treat IVDD. Methods and results. Hydrogel morphology and mechanical properties have been investigated showing high mechanical properties (G'=12kPa) comparable with human native nucleus pulposus (NP) tissue (G'=10kPa), along with ease of handling and injectability in dry and body fluid conditions. Hydrogel nanocomposites resulted biocompatible for the encapsulation of bovine NP cells, showing higher viability (>80%) and metabolic activity in 3D cell culture over 7 days, compared to GO-free hydrogels. Moreover, GO has demonstrated to bind TGF-β3 biomolecules with high efficiency, suggesting the use of GO as local reservoir of growth factors within the injected hydrogel to promote extracellular matrix deposition and tissue repair. Conclusions. Our results show that incorporation of GO within the SAPH improves cell viability and metabolic activity. Furthermore, its tissue-mimicking mechanical properties and chemical tunability make it a promising candidate as injectable carrier of NP cells for the treatment of IVDD. Part of this work has been published (DOI: 10.1016/j.actbio.2019.05.004). Conflicts of interests: No conflicts of interest. Sources of funding: The authors thank the EPSRC & MRC CDT in Regenerative Medicine for its financial support (EP/L014904/1)

Aims

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

Introduction. Elastic fibres are constructed of a central core of elastin surrounded by microfibrils that are composed mainly of fibrillin-1 and fibrillin-2. Patients with mutations in the gene encoding fibrillin-1 or fibrillin-2 develop Marfan syndrome or Beals syndrome (congenital contractural arachnodactyly), respectively. Scoliosis is one of the clinical manifestations in these patients, but how a defect in the elastic proteins could lead to a spinal deformity is not clear. On the one hand, the mutations could induce scoliosis via mechanical means as they could lead to alterations in the biomechanics of the elastic fibre system. On the other hand, elastic fibres also bind growth factors such as transforming growth factor β (TGFβ) and bone morphogenic proteins (BMPs), and the mutations could hence change patterns of spinal growth. Methods. We have investigated the localisation of elastic proteins in different spinal tissues at different stages of curve development in mouse models and in human tissue obtained during scoliosis surgery. Results. Elastic proteins were observed not only in the spinal connective tissues such as ligaments and intervertebral discs, but also in muscle and the bone matrix. The distribution of the different elastic proteins was tissue specific. Additionally, elastic proteins were also detected in the matrix of the vertebral-body growth plates (figure), which has not been reported previously. Conclusions. These observations suggest that elastic proteins could have several functions in the spinal column. Their presence and organisation in the growth plate suggests that they could play an important part in orchestration of spinal growth; a fibrillin mutation-induced malfunction in this regard could be a factor in the development of scoliosis

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.

Aims

The prevalence of scoliosis is not known in patients with idiopathic short stature, and the impact of treatment with recombinant human growth hormone on those with scoliosis remains controversial. We investigated the prevalence of scoliosis radiologically in children with idiopathic short stature, and the impact of treatment with growth hormone in a cross-sectional and retrospective cohort study.

Background. We have reported an injectable L-pNIPAM-co-DMAc hydrogel with hydroxyaptite nanoparticles (HAPna) which promotes mesenchymal stem cell (MSC) differentiation to bone cells without the need for growth factors. This hydrogel could potentially be used as an osteogenic and osteoconductive bone filler of spinal cages to improve vertebral body fusion. Here we investigated the biocompatibility and efficacy of the hydrogel in vivo using a proof of concept femur defect model. Methods. Rat sub-cut analysis was performed to investigate safety in vivo. A rat femur defect model was performed to evaluate efficacy. Four groups were investigated: sham operated controls; acellular L-pNIPAM-co-DMAc hydrogel; acellular L-pNIPAM-co-DMAc hydrogel with HAPna; L-pNIPAM-co-DMAc hydrogel with rat MSCs and HAPna. Following 4 weeks, defect site and organs were histologically examined to determine integration, repair and inflammatory response, as well as Micro-CT to assess mineralisation. Results. No inflammatory reactions or toxicity were seen in any animal. Enhanced bone healing was observed in aged exbreeder female rats where hydrogel was injected with increased deposition of collagen type I. Integration of the hydrogel with surrounding bone was observed without the need for delivered MSCs; native cell infiltration was also seen and bone formation was observed within all hydrogel systems investigated. Conclusion. This novel hydrogel is biocompatible, facilitates migration of cells, promotes increased bone formation and integrates with surrounding bone. This system could be injected to fill spaces within and surrounding spinal cages to aid in cage fixation and spinal fusion without the need for harvesting of bone autografts, thus reducing operative risk and surgical cost. Conflicts of Interest: None. Source of Funding: BMRC, MERI Sheffield Hallam University

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

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.

Background. Intervertebral disc (IVD) degeneration is a major cause of Low back pain (LBP). We have reported an injectable hydrogel (NPgel), which following injection into bovine NP explants, integrates with NP tissue and promotes NP cell differentiation of delivered mesenchymal stem cells (MSCs) without growth factors. Here we investigated the injection of NPgel+MSCs into bovine NP explants under degenerate culture conditions to mimic the in vivo environment of the degenerate IVD. Methods. hMSCs were incorporated within liquid NPgel and injected into bovine NP explants alongside controls. Explants were cultured for 6 weeks under hypoxia (5%) with ± calcium 5.0mM CaCl. 2. or IL-1β individually or in combination to mimic the degenerate microenvironment. Cell viability was assessed by caspase 3 immunohistochemistry. Histological and immunohistochemical analysis was performed to investigate altered matrix synthesis and matrix degrading enzyme expression. Results. CFSe positive hMSCs were identified in all NPgel injected explants and cell viability was maintained. The NPgel integrated with NP tissue and hMSCs produced matrix components: aggrecan, collagen type II and chondroitin sulphate in standard and degenerate culture conditions. Increased cellular immunopositivty for aggrecan and collagen type II as well as decreased cellular immunopositivity for degrading enzyme expression was observed within NP tissue removed from the injection site. Conclusion. MSCs incorporated within NPgel could be used to regenerate the NP and restore the healthy NP phenotype of degenerate NP cells as a treatment strategy for LBP. We are currently investigating the survival and differentiation capacity of hMSCs delivered via the NPgel into degenerate human NP explants and thus ascertain the future clinical success of this therapy. Conflicts of Interest: None. Funding: BMRC, MERI Sheffield Hallam University

Background. Degeneration of the intervertebral disc (IVD) is a major cause of Low back pain. We have recently reported a novel, injectable liquid L-pNIPAM-co-DMAc hydrogel (NPgel), which promote differentiation of MSCs to nucleus pulposus (NP) cells without the need for additional growth factors. Here, we investigated the behaviour of hMSCs incorporated within the hydrogel injected into NP tissue. Methods. hMSCs were injected either alone or within NPgel, into bovine NP tissue explants and maintained at 5% O. 2. for up to 6wks. Media alone and acellular NPgel were also injected into NP explants to serve as controls. Cell viability was assessed by Caspase 3 immunohistochemistry and the phenotype of injected hMSC was assessed by histology and immunohistochemistry. Mechanical properties were also assessed via dynamic mechanical analysis (DMA). Results. No significant difference in the elastic modulus was observed between NPgel injected NP tissue and media injected controls. CFSe positive hMSCs were identified in all injected tissue samples and cell viability was maintained. Where hMSCs were delivered via NPgel, the hydrogel integrated with native NP tissue and cells producing NP matrix components: aggrecan; collagen type II and chondroitin sulphate. Conclusion. hMSC incorporated within L-pNIPAM-co-DMAc hydrogel and injected into NP explants, integrate with native NP tissue and promote differentiation towards the NP phenotype; thus potentially could be used to regenerate the NP as a treatment strategy for LBP. No conflict of interest. Funding: BMRC, MERI Sheffield Hallam University

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.

Introduction. Marfan syndrome (MFS) is a common connective tissue disorder affecting one in 3300 people worldwide, and is caused by unique mutations in the 65 exon gene for fibrillin-1—an essential microfibril component of ligaments, tendons, and muscle. A recently discovered feature in the Marfan mouse model is increased concentrations of transforming growth factor β, resulting in overgrowth. 70% of patients with MFS have scoliosis of some degree. Can lessons be learned from MFS aetiology and treatment that apply to idiopathic adolescent scoliosis? We aimed to establish whether there is a relationship between the type and location of mutation, and the presence and degree of severity of scoliosis, in patients with MFS. Methods. Of 181 consecutive patients with MFS with known causative fibrillin-1 mutations, 93 were male (51%) and 88 female (49%). 28 (15%; ten males, 18 females) of the total group had moderate to severe scoliosis, including two females and two males who had corrective surgery. Of the 16 patients with severe scoliosis (three males, 13 females), FBN1 mutations clustered in the latter half of the gene in exons 33–63. Of these 16 mutations, ten were severe (seven stop codons, three splice site mutations); the others were point mutations, three involving added cysteine and three substituted cysteine, in calcium-binding EGF-like regions. Height A rapid adolescent growth spurt to excessive height is a documented clinical feature in MFS. The age of clinical diagnosis as an indication of severity was on average 11·3 years (range 2 days to 36 years), and ten patients were diagnosed before the age of 12 years. Conclusions. Genotype-phenotype correlation for patients with MFS with moderate to severe scoliosis shows the trend/association of severe mutations in 25%, with 50% of the total in the latter half of the gene (exons 33–63) with stop codons and splice site mutations. Cysteine substitutions in calcium binding EGF-like regions occurred in a further 25% of mutations. Disruption of spinal support together with rapid excessive early pubertal growth presents a human model for production of scoliosis, and a rationale for attempted preventive irbesartan therapy in Marfan mouse models and human patients. The 21-centre national AIMS Trial of irbesartan in MFS commences in January, 2011, and skeletal measurements will be of interest

Introduction. Given the predominant functional role which aggrecan has in the intervertebral disc, particularly within the nucleus pulposus, it is necessary to evaluate the quality of aggrecan produced by cells within tissue engineered disc constructs. The aim here was to characterise the nanostructure of aggrecan synthesised by nucleus pulposus cells treated with growth differentiation factor [GDF]-6) seeded in hydrogels in comparison to aggrecan isolated from healthy disc. Methods. Aggrecan was isolated from bovine nucleus pulposus (NP) tissue (n=3 [<18 months old]) and primary bovine NP cells cultured with (+GDF6) or without GDF6 (−GDF6) for 28 days (n=2) in type I collagen hydrogels. Isolated aggrecan monomers were visualised by atomic force microscopy and categorised as either intact (globular domains visible at both the N and C termini) or non-intact. Core protein contour length (L. CP. ) was calculated for intact molecules. The proportion of non-intact/fragmented to intact aggrecan and the molecular area of all monomers was determined. Results. Very few aggrecan molecules were intact (1.3% in NP compared to 4.3% +GDF6 and 0% -GDF6). There was no significant difference in the mean L. CP. between NP (389 ± 37 nm) compared to +GDF6 (379.2 ± 26 nm) or the molecular area between NP (3560 ± 2179 nm. 2. ) and –GDF6 (3586 ± 2071 nm. 2. ). However, the molecular area in both cases was significantly lower than +GDF6 (4774 ± 3715 nm. 2. ) p≤0.0001. Discussion & conclusions. Aggrecan structure can be altered by culture conditions. GDF6 treatment promoted the synthesis of more intact monomers, with greater over all molecular area. Conflicts of interest: None. Funding: Impact Research Scholarship and the Presidents Doctoral Scholarship, provided by the University of Manchester

Introduction. Spinal deformations are a deviation of the natural arrangement of forces during growth. Environmental factors play a part in these deviations. The presence of lordosis in the thoracic spine is a causative factor in spinal deformations that needs to be addressed. Most biomechanical models of bracing have a scientific background. Has older knowledge lost its value? In living structures, all processes such as regulation of equilibrium in posture and movement use Newton's law and extended laws of Hooke for conservation of energy, momentum, and angular momentum under control of the central nervous system. Form follows function (phylogenetic and ontogenetic) in the spine as primary engine in movement in animals. The change in function in bipedals is that the coupling mechanism at the thoracolumbar joint now couples a reversed pendulum. Methods. A literature search shows a clear gap in the evolution in science on deformities during 1914–45. In 1792, Van Gesscher postulated two concepts in Observations on Deformations of the Spine (Dutch). First, the optimalisation of the balancing forces in men needs a specific optimum curvature to keep the weight of the head and shoulders above the hips. The second concept was the role of sitting in relation to changes around the discs at the thoracolumbar spine. Girls who read or knitted while sitting developed scoliosis more easily than did others. His extending (by lordosis) corrective corset was used for more than 150 years before plaster became popular. Andry described guidance and correction of growing spines with use of the moulding capability of muscular forces, with exercises and extending corsets (for so-called weak girls). Extension and avoidance of incorrect posture during sitting became a mainstay in orthopaedics (and schools). In 1907, Wullstein described experiments in young dogs to show how forced fiexion produces all characteristics of kyphotic deformities. In 1912, Murk Jansen did a critical review of all available knowledge and his own research in The Physiologic Scoliosis and its causes. Post mortem studies showed anatomical asymmetry in the left and right crura of the diaphragm, which indicated that asymmetric rotational forces in ventilation could induce predominant lateral curves. In-vivo tests show increased thoracolumbar kyphosis if siblings are put in seated positions too frequently and too soon. The stiffening in kyphosis creates a fulcrum to cantilever the opposing rotational forces to lateral curvatures. In experiments in rabbits, lower intrathoracic pressure was shown in the right pleural cavity. Common alertness of parents and teachers was underwritten. Some of this still survives. In progressed scoliosis, Sayre's method of corrective plastering in suspension and Calot's corrections in prone position under anaesthesia and plaster shelves with lordosis in bed became popular. In the Volkmann Hueter principle, the resilience of the deformable structures in the spine were identified–eg, the discs, the apophyses, and the cartilage in joints have a role in spinal deformity. Cobb drew attention to the clinical aspects of scoliosis. Roth provided a comprehensive explanation of how growth is organised and regulated by the oldest organ of animal life: the central nervous system in vertebrates. Between 1960 and 1985, Roth developed his concepts on neurovertebral and neuro-osseous growth relations and the tension-driven incongruence of growth. Roth provided new biological knowledge about how growth seems to support older clinical observations. In animal experiments, mechanical modelling, and radiological studies in scoliosis he stressed the role that growth has in the formation of the spine. A so-called short cord can indeed cause scoliosis. Recent studies with MRI in idiopathic scoliosis confirm this hypothesis. Personal observations In 2008, a study showed that forceful restoration of thoracolumbar lordosis can correct double major scoliotic curves. A consequent thoracolumbar kyphotic curve was found, and recently reproduced. The thoracolumbar lordotic intervention brace technique showed promising results. It relied on the older techniques, leaving only the fear for lordosis brought by Dickson. In personal observations, the presence of neuromuscular tightness or tension also present in progressive scoliosis as representatives of deforming and protective forces. Conclusions. Previous knowledge depicts spinal growth as result of a combination of neuro-osseous growth regulation in a very complex but understandable loco-motor system, in which external factors cause muscular reaction that obey all mechanical laws. Lifestyle factors seem to greatly affect deformations

Mesenchymal stem-cell based therapies have been proposed as novel treatments for intervertebral disc degeneration, a prevalent and disabling condition associated with back pain. The development of these treatment strategies, however, has been hindered by the incomplete understanding of the human nucleus pulposus phenotype and by an inaccurate interpretation and translation of animal to human research. This review summarises recent work characterising the nucleus pulposus phenotype in different animal models and in humans and integrates their findings with the anatomical and physiological differences between these species. Understanding this phenotype is paramount to guarantee that implanted cells restore the native functions of the intervertebral disc.

Cite this article: Bone Joint Res 2013;2:169–78.