Cell transplantation in lumbar spine disc degeneration disease

Abstract

Low back pain is an extremely common symptom, affecting nearly three-quarters of the population sometime in their life. Given that disc herniation is thought to be an extension of progressive disc degeneration that attends the normal aging process, seeking an effective therapy that staves off disc degeneration has been considered a logical attempt to reduce back pain. The most apparent cellular and biochemical changes attributable to degeneration include a decrease in cell density in the disc that is accompanied by a reduction in synthesis of cartilage-specific extracellular matrix components. With this in mind, one therapeutic strategy would be to replace, regenerate, or augment the intervertebral disc cell population, with a goal of correcting matrix insufficiencies and restoring normal segment biomechanics. Biological restoration through the use of autologous disc chondrocyte transplantation offers a potential to achieve functional integration of disc metabolism and mechanics. We designed an animal study using the dog as our model to investigate this hypothesis by transplantation of autologous disc-derived chondrocytes into degenerated intervertebral discs. As a result we demonstrated that disc cells remained viable after transplantation; transplanted disc cells produced an extracellular matrix that contained components similar to normal intervertebral disc tissue; a statistically significant correlation between transplanting cells and retention of disc height could displayed. Following these results the Euro Disc Randomized Trial was initiated to embrace a representative patient group with persistent symptoms that had not responded to conservative treatment where an indication for surgical treatment was given. In the interim analyses we evaluated that patients who received autologous disc cell transplantation had greater pain reduction at 2 years compared with patients who did not receive cells following their discectomy surgery and discs in patients that received cells demonstrated a significant difference as a group in the fluid content of their treated disc when compared to control. Autologous discderived cell transplantation is technically feasible and biologically relevant to repairing disc damage and retarding disc degeneration. Adipose tissue provides an alternative source of regenerative cells with little donor site morbidity. These regenerative cells are able to differentiate into a nucleus pulposus-like phenotype when exposed to environmental factors similar to disc, and offer the inherent advantage of availability without the need for transporting, culturing, and expanding the cells. In an effort to develop a clinical option for cell placement and assess the response of the cells to the post-surgical milieu, adipose-derived cells were collected, concentrated, and transplanted under fluoroscopic guidance directly into a surgically damaged disc using our dog model. This study provides evidence that cells harvested from adipose tissue might offer a reliable source of regenerative potential c...

Mesenchymal progenitor cells combined with pentosan polysulfate mediating disc regeneration at the time of microdiscectomy: a preliminary study in an ovine model

“…1,2,10,16,20,22,25,[30][31][32][34][35][36][37][38]46,48,49,53,54,56,57,60,62,[64][65][66][67]69,73,83,90 The EuroDISC study, by Meisel and colleagues, 49 investigated the percutaneous transplantation of autologous disc chondrocytes. Following microdiscectomy, disc chondrocytes were harvested and expanded in vitro and were subsequently injected into the NP 3 months postoperatively.…”

Médecine régénératrice du disque intervertébral

“…L'utilisation de cellules du NP issues de DIV sains étant impossible du fait de la morbidité associée au prélèvement, des cellules provenant de DIV herniés ont fait l'objet d'investigations précliniques et cliniques avec des résultats satisfaisants [12]. Ainsi, chez l'animal, mais également chez …”

“…Parfois imparfaites, notamment par l'absence d'uniformité entre les matériels et les méthodes, ces études précliniques ont malgré tout permis d'envisager la mise en oeuvre d'études cliniques. Une étude avec des cellules autologues du NP (isolées d'un DIV hernié adjacent) cultivées pendant 12 semaines avant leur réimplantation montre à deux ans, au niveau morphologique, une restauration des signaux IRM reflétant l'état d'hydratation du tissu discal et une réduction des douleurs (essai EuroDisc chez environ 60 patients) [12]. Dans une autre étude, ayant pour objectif de traiter 15 patients avec des chondrocytes L'ingénierie tissulaire L'ingénierie tissulaire a pour principe l'utilisation de cellules associées à un biomatériau ou à une matrice.…”

In vitro extracellular matrix accumulation of nasal and articular chondrocytes for intervertebral disc repair

“…While artificial disc and nucleus implants are effective in select patient populations, these surgical approaches are highly invasive and fail to address the underlying degenerative changes resulting in back pain. Wherein underlying cellular dysfunction results in functional loss, cellular-based implantation therapies have been proposed for the treatment of degenerated IVD with the aim of delivering cells to repopulate the nucleus pulposus (NP) region, augment tissue repair and restore functionality (Anderson et al, 2005;Benneker et al, 2014;Hohaus et al, 2008;Miot et al, 2012;Oehme et al, 2015).…”