In a recent study that came out earlier this month, researchers discussed the current status of cell therapy in clinical trials and the potential application towards treatment of patients suffering from spinal injuries and symptoms caused by intervertebral disc degeneration.[1]
Intervertebral disc degeneration is a major cause of neck and low back pain, effecting 632 million people worldwide.[2] In many of those suffering from chronic neck or back pain, conservative therapy or surgery has not provided a satisfactory outcome, so there is a clear need for new therapies to address disc degeneration and restore disc function. This has led to significant research and advances in tissue engineering in the last decade.
Currently, there are three biological approaches in cell therapy research: stimulating anabolic process, modulating catabolic processes and providing new cells. The new cell approach seems to be getting the most attention since an important feature of intervertebral disc degeneration is a decrease in the number of viable and functional cell numbers. The study indicates that stem cell research appears promising (both in mobilizing stem cells from surrounding tissues or direct implantation of stem cells into the damaged disc), in that in vivo studies have demonstrated that stem cells are able to survive and proliferate after implantation into the disc and also are able to suppress inflammatory reactions in the tissue. However, there are also serious concerns associated with stem cell transplantation, including poor cell survival and leakage through the injection site, as well as the potential for bone weakness and tumor growth.
Despite the potential risks, there is strong data to suggest that cell therapy can influence early degenerative changes. What is still unknown is at what stage of degeneration that cell therapy will be helpful and for how long cell therapy will stop disease progression. In a recent European study, researchers injected culture-expanded autologous disc cells to patients with disc herniations. Two years later, the treatment group reported significant pain reduction, preservation of disc height at the treated level and maintenance of hydration in adjacent levels.[3] Another clinical study using the NuQu cartilage cell system was performed on 15 patients with single level moderate lumbar disc degeneration, resulting in continued improvement in pain scores as well as improved or unchanged MRI results in a one year period.[4]
The researchers indicate that one of the most difficult questions is to how to be able to define the level of disc degeneration that is beyond biological repair, but they were able to identify several conditions that were good candidates for cell therapy in disc repair: (1) discogenic pain from annular injured discs with high intensity zones; (2) prevention of adjacent segment disease; and (3) prevention of post-discectomy syndrome.
For patients suffering from discogenic pain caused by annular injured discs with high intensity zones, cell therapy seems promising because the annular fibrosis, while damaged, has not lost its ability to withstand hydrostatic pressure and no relevant structural changes have occurred. In addition, discogenic pain has an inflammatory component where introduction of metabolically active cells may have a positive effect. The researchers indicate that cell therapy for an annular injured disc would be beneficial if the condition is recognized early enough to be effective, which unfortunately is not often the case when the patient takes conservative approaches to manage discogenic pain.
Adjacent segment disease frequently occurs to discs that are adjacent to a fused disc. These discs will degenerate at a faster rate than normal and can likely become symptomatic over time. Since these patients are already under the care of a spine surgeon, they are excellent candidates for cell therapy at the adjacent segment. A phase I study is currently ongoing in Japan regarding cell therapy to prevent intervetebral disc degeneration in the adjacent disc. The treatment group is patients in their 20s undergoing fusion surgery. In that study, scientists culture nucleus pulposus cells from the disc undergoing fusion surgery and then culture those cells with autologous mesenchymal stem cells from the bone marrow and then inject the material to the disc adjacent to the fusion level. Results from this study are still pending, but preliminary results show no major issues with patient safety.
Partial discectomy is a common and effective procedure for disc herniation and can be effective with regard to neurologic symptoms arising from the herniated disc, but it fails to address the altered biomechanical properties of the segment and annular defect. If all, or most, of the nucleus pulposus is resected, there is a significant chance that lost biomechanical function could lead to further instability or collapse of the segment. The study indicates that both synthetic and natural biomaterials capable of restoring functional biomechanics of the intervertebral disc are under development and offer promise.[5] Because a successful regeneration of both the annulus and the nucleus must meet mechanical and biological compatibility, it is thought that cell therapy for annular repair may be helpful to overcome this difficulty.
The researchers acknowledge that while the success of cell therapy in an environment with limited nutrient supply and transport of metabolites is unknown, they cite several reasons for using a cell therapy approach to regenerate the disc:
a) In degenerated discs, a reduced number of cells have been found in affected specimens that cannot be explained by limited nutrition and aging alone;
b) Similarly, a loss of cells and matrix has been observed in disc herniations, further limiting the healing potential of the ruptured AF;
c) The effect of application of growth factors or other pharmaceuticals to regenerate the disc is temporally limited and may require several repetitive interventions or sustained release formulations, whereas the duration of cell-based therapies depends on the survival and activity of the cells. Hence, a single stage application can have a long-lasting effect; and
d) Cells can fulfill several functions, including matrix production, prevention of AF deformation, inflammation control, production of growth factors and prevention of angio- and neuro-genesis. Eventually, cells have the potential to interact with the resident cell population, regulate local homeostasis and attract additional cells.[6]
The attorneys at Adler Giersch, PS will continue to monitor these studies and will provide updates as they are available. We remain committed to informing our readers and the community about advances in the medical research in this area, as it helps us to be better advocates for our clients and to ensure that they receive the best and most current care available. If you or your patients need legal guidance following a traumatic injury simply give us a call. Our initial consultations are confidential and free.
[1] “Cell therapy for intervertebral disc repair: advancing cell therapy from bench to clinics” Benneker LM, Andersson G, Iatridis JC, Sakai D, Härt R, Ito K, Grad S; Eur Cell Mater. 2014 May 6;27:5-11.
[2] Ibid.
[3] “Clinical experience in cell-based therapeutics: disc chondrocyte transplantation. A treatment for degenerated or damaged intervertebral disc;” Meisel HJ, Siodla V, Ganey T, Minkus Y, Hutton WC, Alasevic OJ; (2007) Biomol Eng 24: 5-21.
[4] ” Porcine intervertebral disc repair using allogeneic juvenile articular chondrocytes or mesenchymal stem cells;” Acosta FL Jr, Metz L, Adkisson HD, Liu J, Carruthers- Liebenberg E, Milliman C, Maloney M, Lotz JC; (2011) Tissue Eng Part A 17: 3045-3055.
[5] “Role of biomechanics on intervertebral disc degeneration and regenerative therapies: What needs repairing in the disc and what are promising biomaterials for its repair;”James C. Iatridis, Steven B. Nicoll, Arthur J. Michalek, Benjamin A. Walter, and Michelle S. Gupta; Spine J. Mar 2013; 13(3): 243–262.
[6] “Cell therapy for intervertebral disc repair: advancing cell therapy from bench to clinics” Benneker LM, Andersson G, Iatridis JC, Sakai D, Härt R, Ito K, Grad S; Eur Cell Mater. 2014 May 6;27:5-11.
