Back pain (BP) is a common clinical condition that leads to high morbidity with significant psychosocial and economic effects. It is the leading cause of disability in people under 45 years of age, and it results in enormous national economic losses in developed countries. The wide majority of BP is associated with degenerative changes of the intervertebral disc (IVD). Intervertebral disc degeneration (IVDD) is an age-related chronic process that is characterized by a progressive reduction of proteoglycans and water content in the nucleus pulposus (NP) with loss of the IVD's ability to resist compressive forces. Current treatment options for BP and IVDD range from conservative measures to invasive procedures however, these treatment modalities have limited efficacy and do not produce predictable and reliable outcomes. Therefore, there is a clear need for more effective early treatments of BP that may prevent, slow down, or reverse the degenerative changes. To evaluate the efficacy of novel IVD regenerative treatments, prior to translation into humans, ex vivo and in vivo animal model systems are needed.
In the present study, a novel transpedicular approach to the IVD has been validated in 12 sheep. Under fluoroscopy, a 2-mm Kirshner wire was introduced through the vertebral body with a inclination of approximately 45° in all plans direction to reach the center of the NP. In each animal, four IVDs, from L1 to L5, were addressed by performing different surgical techniques respectively: (I) nucleotomy, (II) tunnel, (III) nucleotomy + polyurethane (PU) scaffold, and (IV) tunnel + PU scaffold. Intact IVDs (L5-6) were used as controls. Intra- and post-surgical morbidity rates were low; CSF leakage was recorded in two spinal segments whereas discospondylitis and vertebral luxation occurred respectively at L1-2 and L3-4 in two different animals. The quantitative and qualitative analysis of MRI, radiologic, histologic and macroscopic data, collected at four different time points (before and 1, 3 and 6 months after surgery), suggested that the injury induced in the present model represents a reliable method for initiating a progressive IVDD process, obtaining different degrees of IVDD depending on the type of lesion performed. The endplate damage itself, caused by the realization of the transpedicular tunnel, led to IVD degenerative changes, although to a lesser extent than those caused by performing nucleotomy. Furthermore, the sealing of the tunnel with the PU scaffold resulted in a lack of cells leakage throughout the tunnel.
The transpedicular approach represents a feasible alternative route to the IVD, without causing damage to the annulus fibrosus. This new pathway to the IVD provides a new valid model to study biologic and biomechanical alterations in relation to both IVD degenerative processes and potential NP regenerative therapies.
A 1-year-old sexually intact male Korat cat was referred for ophthalmological consultation due to anisocoria. Mydriasis with external ophthalmoplegia and absence of pupillary light responses in the right eye and nasofacial hypalgesia were seen. Cavernous sinus syndrome (CSS) was suspected. Bilateral deformities of the jaw and phalangeal bones, severe spinal pain and abnormal conformation of the lumbar spine were also present. Radiographic examination revealed several mineralised masses in the appendicular and axial skeleton, indicative of multiple cartilaginous exostoses. For further investigation of the CSS-related neurological deficits, the cat underwent computed tomography (CT) examination of the skull. CT images revealed a non-vascularised, calcified, amorphous mass originating from the right lateral skull base and superimposing on the sella turcica. Based on the severity of diffuse lesions and owing to the clinical signs of extreme pain, the cat was euthanased. A diffuse skeletal and intracranial osteochondromatosis was diagnosed histologically.
IntroductionTo study the efficacy of novel regenerative strategies is necessary to develop new models that do not implement annulus fibrosus (AF) damage. We hypothesize an ideal preclinical model to study novel biological therapies for nucleus pulpous (NP) regeneration can be achieved by approaching the NP via the endplate (EP) route through a minimal invasive transpedicular approach.1 The aim of the study is to characterize a preclinical ovine model triggering EP damage and repair with or without mechanical nucleotomy, while keeping the AF intact. Material and MethodsSheep (n = 12, 3 years old), were used. Throughout the transpedicular approach, a 2mm tunnel was drilled to the NP. Nucleotomy was performed using a shaver resector. The tunnel was sealed using a press-fit porous polyurethane (PU) cylinder. Five lumbar discs were assigned to different groups: EP tunnel (A); EP tunnel + nucleotomy (B); EP tunnel + repair with PU scaffold (C); EP tunnel + nucleotomy + repair (D); no treatment (E). X-ray and MRI was performed at 0, 1, 3 and 6 mths after. Disc height and MRI indexes were calculated and disc macro- and micro-morphology were analyzed. MRI images and gross anatomy photographs were graded using both Pfirrmann2 and Thompson3 grading systems. ResultsMRI analysis showed a progressive decrease of NP signal intensity with different degrees of degeneration. According to Pfirrmann degenerative grade, the C group showed a grade II, group A appeared as grade III, group D looked as grade IV and group B appeared as grade V. Morphologically, all stages of the degenerative process from Thompson grade I to grade V were also observed with the same association. Histological analysis revealed progressive disc narrowing, fragmentation of the NP matrix in D and B group. The scaffold in the tunnel of C and D groups appeared colonized by cells without sign of bone formation at all time point. NP tissue was in the tunnel with infiltration of inflammatory cells in A and B groups. ConclusionA new preclinical model to study tissue-engineering strategies for NP regeneration has been developed and characterized by approaching the NP via the EP route through a minimal invasive transpedicular approach [1]. Keeping the AF intact, the different degrees of IDD have been observed according to Pfirrmann and Thompson grading system. The sealing of the tunnel prevents the NP to leak out of the disc space.This represents a significant contribution toward the translation of new regenerative strategies for biological restoration of early and mild IVD degenerative. AcknowledgmentThe support of the Italian Ministry of Instruction, University and Research Grant (PRIN-200938NT8Z), the Young Investigator Research Grant of the Italian Ministry of Health (GR-2010–2318448) and the BIOSPINA Award of the Italian Society of Spine Surgery (SICV&GIS) are gratefully acknowledged.ReferencesVadalà G, Russo F, Pattappa G, et al. The transpedicular approach as an alternative route for intervertebral disc regeneration. Spine 2013;38(6):E319–E324Pfirrmann CW, Metzdorf A, Zanetti M, Hodler J, Boos N. Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine 2001;26(17):1873–1878Thompson JP, Pearce RH, Schechter MT, Adams ME, Tsang IK, Bishop PB. Preliminary evaluation of a scheme for grading the gross morphology of the human intervertebral disc. Spine 1990;15(5):411–415
A 16-year-old neutered female domestic shorthair cat was referred for chronic history of reluctance to jump, stiffness of the tail and lower back pain. Mild pelvic limb ataxia, reduced perianal reflex and lumbosacral discomfort were present on neurological examination. On magnetic resonance imaging, a well-defined rounded structure of 3 mm in diameter was identified on the right dorsal aspect of the epidural space at L7-S1, causing displacement of the cauda equina. The lesion was hyperintense to spinal cord parenchyma on T2-weighted images and hypointense on T1-weighted images, consistent with a fluid-filled structure. A Lumbosacral dorsal laminectomy was performed. A clear fluid-containing structure was identified between the right L7 nerve root and the cauda equina. Following surgical excision, histopathology confirmed the cystic nature of the lesion and revealed thick disorganised sheaths of fibrocollagenous tissue and flattened mesenchymal cells lining the luminal part of the cyst wall. A diagnosis of intraspinal ganglion cyst was made. The cat recovered uneventfully. Seven months after surgery euthanasia was performed for unrelated reasons; no neurological deficits were present.This is the first reported case of intraspinal ganglion cyst in a cat. Intraspinal extradural cysts should be considered among other differential diagnoses for cats with lumbosacral myelopathy/radiculopathy.
BackgroundStem cell based intervertebral disc (IVD) regeneration is quickly moving towards clinical applications. However, many aspects need to be investigated to routinely translate this therapy to clinical applications, in particular, the most efficient way to deliver cell to the IVD. Cells are commonly delivered to the IVD through the annulus fibrosus (AF) injection. However, recent studies have shown serious drawbacks of this approach. As an alternative we have described and tested a new surgical approach to the IVD via the endplate-pedicles (transpedicular approach). The Purpose of the study was to test MSCs/hydrogel transplantation for IVD regeneration in a grade IV preclinical model of IDD on large size animals via the transpeducular approach with cell dose escalation.MethodsAdult sheep (n=18) underwent bone marrow aspiration for autologous MSC isolation and expansion. MSC were suspended in autologous PRP and conjugated with Hyaluronic Acid and Batroxobin at the time of transplant (MSCs/hydrogel). ...
