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 disc-derived 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 capable of bio-restitution.

Fig. 1

Gross pathology 12 month follow-up after autologous chondrocyte transplantation in the Canine model Level L3–L4 was transplanted, level L1–L2 received no treatment and displayed more scar tissue, L2–L3 was the control level with a normal intervertebral disc

Fig. 2

Staining of paraffin sections of the regenerated intervertebral disc 6 months following cell transplantation. BrdU containing chondrocytes were detected and stained by immunohistochemical procedures using DAB as the chromogen. Sections were counterstained by Eosin. BrdU positive cells are colored black. a Nucleus regenerate overview (25×), b BrdU stained transplanted cells (200×), c, d single BrdU stained transplanted chondrocytes, pericellular de novo synthesis of nucleus matrix (1,000×)

Fig. 3

Intraoperative picture of the fluoroscopic guided minimal invasive puncture of the intervertebral disc form the opposite side, pressure–volume-test and transplantation

Fig. 4

28 years old woman undergoing discectomy in level L5–S1. The 60-month follow-up in the MRI displays the stable disc high in the transplanted level L5–S1. a Pre transplantation, b 1 day post transplantation, c 3-month post transplantation, d 12-month post transplantation, e 24-month post transplantation, f 60-month post transplantation

Fig. 5

6-month follow-up with MRI sagittal section (same dog as in Fig. 2)

Fig. 6

6-month follow-up gross section pathology a L3–L4 no treatment, b L4–L5 hyaluronic acid alone, c L5–L6 adipose-derived stem cells in hyaluronic acid, d L6–L7 normal disc

Fig. 7

Cell viability and cell sustenance were judged positive by DAPI-stained nuclei that were present 6-month following transplantation of the adipose-derived stem cells