Intervertebral Disc Degeneration


            Intervertebral discs (IVDs) are the rubbery, collagenous cushions that separate bones in a spine.  They absorb shock and allow motion.  When they degenerate they can lose integrity and bulge outward, pressing on the spinal cord and causing chronic back pain.  Back pain is a highly prevalent health condition, and yet study of its causes and solutions is hampered by a lack of good animal models for the human spine.  We humans walk on two legs and experience the compressive force of gravity on our IVDs.  An animal walking on four legs does not.  Likely due to this difference in compressive forces experienced, animals don’t develop spontaneous age-related disc degeneration the way humans do.  Finally, human discs are much larger than a typical lab animal’s.  This is a significant problem because IVDs are avascular and rely on diffusion and bulk fluid flow to deliver nutrients to their cells.  A large disc presents a much greater challenge to diffusion than a small disc.  For these reasons, the efficacy of surgical spinal implants such as artificial discs and disc-sparing devices cannot currently be assessed in animals before testing in humans.

 To address this problem we are working with Dr. Anton Bowden, a spine specialist in the BYU Department of Mechanical Engineering, to characterize a potential new animal model.  Camelids such as llamas and alpacas, while walking on four legs, have very long, upright necks that experience significant compressive forces.  They also have a curve at the base of the neck that resembles the lordotic curvature in the lumbar region of the human spine.  A thorough biomechanical analysis of alpacas revealed that their IVDs are more like humans in size, structure, and flexibility than any previously studied animal model [1].  To determine whether alpacas experience spontaneous age-related disc degeneration like humans do, we performed MRI scans of 20 alpacas from a local farm.  We found evidence of advanced disc degeneration in 47% of the alpacas that were over 10 years old, while those less than 6 years old showed no disc degeneration.  Degeneration was most common in the two lowest cervical discs—those located in the curve at the base of the neck [2].  These results suggest that alpacas may be a feasible pre-clinical model for testing human spinal implants.  Our next goal is to complete development of a set of alpaca-specific qRT-PCR primers that target genes relevant to disc degeneration and regeneration.  These will allow us to characterize the disc degeneration at the molecular level so that we can then identify successful surgical  implants by their ability to halt or reverse the gene expression changes associated with IVD degeneration.

In a parallel effort to improve our ability to study IVDs, we are engineering a dynamic bioreactor for keeping IVDs and their adjacent vertebral bones alive outside the body for an extended period of time.  This dynamic bioreactor applies bending and compressive forces that mimic the movement of a human spine, to draw nutrients from the culture medium into the disc and to expel wastes from it the way motion (rather than blood flow) provides nutrients to IVDs in the body [3].  We are currently working to optimize the device to improve sterility, nutrient exchange, and gas exchange.  Ultimately, we intend to use this device to study the progressive changes in gene expression that accompany the process of IVD degeneration.       

 Publications

 1.  Stolworthy DK, Fullwood RA, Merrell TM, Bridgewater LC, Bowden AE: Biomechanical analysis of the camelid cervical intervertebral disc. Journal of Orthopaedic Translation 2015, 3:34-43.

2.  Stolworthy DK, Bowden AE, Roeder BL, Robinson TF, Holland JG, Christensen SL, Beatty AM, Bridgewater LC, Eggett DL, Wendel JD et al: MRI evaluation of spontaneous intervertebral disc degeneration in the alpaca cervical spine. J Orthop Res 2015.

3.  Beatty A, Bowden AE, Bridgewater LC: Development of complex dynamic intervertebral disc bioreactor. In preparation 2015.

 Indispensable collaborators

Disc biomechanics and bioreactor design and construction:  Dr. Anton Bowden, BYU Department of Mechanical Engineering
Alpaca sedation and monitoring:  Dr. Beverly Roeder, BYU Department of Biology
Alpaca handling, Dr. Todd Robinson, BYU Department of Plant and Wildlife Sciences
MRI expertise:  Dr. Neal Bangerter, BYU Department of Electrical and Computer Engineering