‘Rumours of my death may have been greatly exaggerated’: a brief review of cell death in human intervertebral disc disease and implications for cell transplantation therapy

2007 ◽  
Vol 35 (4) ◽  
pp. 680-682 ◽  
Author(s):  
W.E.B. Johnson ◽  
S. Roberts

The avascular nature of the human intervertebral disc is thought to reduce the ability of resident disc cells to maintain their extracellular matrix, rendering the tissue susceptible to degeneration. It has also been suggested that the lack of a blood supply may result in disc cell death via nutrient deprivation. Therefore transplanting new cells into the disc to promote tissue regeneration would be akin to ‘putting cells in a coffin’ and doomed to failure. This review considers the available evidence for cell death in the human intervertebral disc, describing briefly the methods used to assay such death, and concludes that further analysis is required to ascertain whether extensive cell death truly is a marked feature of human intervertebral discs and whether it bears any relationship to disc degeneration and hence regenerative strategies.


1973 ◽  
Vol 39 (2) ◽  
pp. 203-208 ◽  
Author(s):  
Dwight Parkinson ◽  
Christopher Shields

✓ Thirty-three intervertebral disc patients who otherwise would have been subjected to surgery were treated by injection with chymopapain. The pharmacology, toxicology, physiology, immunology, and chemical action of this enzyme, which specifically reacts with chondromucoproteins, are discussed. Results indicate that this method, although still experimental and unapproved by the U. S. Food and Drug Administration, may become a useful addition to the surgeon's armamentarium in the treatment of intervertebral disc disease.



2017 ◽  
Vol 114 (43) ◽  
pp. 11476-11481 ◽  
Author(s):  
Emily A. Brown ◽  
Peter J. Dickinson ◽  
Tamer Mansour ◽  
Beverly K. Sturges ◽  
Miriam Aguilar ◽  
...  

Chondrodystrophy in dogs is defined by dysplastic, shortened long bones and premature degeneration and calcification of intervertebral discs. Independent genome-wide association analyses for skeletal dysplasia (short limbs) within a single breed (PBonferroni = 0.01) and intervertebral disc disease (IVDD) across breeds (PBonferroni = 4.0 × 10−10) both identified a significant association to the same region on CFA12. Whole genome sequencing identified a highly expressed FGF4 retrogene within this shared region. The FGF4 retrogene segregated with limb length and had an odds ratio of 51.23 (95% CI = 46.69, 56.20) for IVDD. Long bone length in dogs is a unique example of multiple disease-causing retrocopies of the same parental gene in a mammalian species. FGF signaling abnormalities have been associated with skeletal dysplasia in humans, and our findings present opportunities for both selective elimination of a medically and financially devastating disease in dogs and further understanding of the ever-growing complexity of retrogene biology.



2017 ◽  
Author(s):  
Emily A. Brown ◽  
Peter J. Dickinson ◽  
Tamer Mansour ◽  
Beverly K. Sturges ◽  
Miriam Aguilar ◽  
...  

Chondrodystrophy in dogs is defined by dysplastic, shortened long bones and premature degeneration and calcification of intervertebral discs. Independent genome-wide association analyses for skeletal dysplasia (short limbs) within a single breed (pBonferroni=0.0072) and intervertebral disc disease (IVDD) across breeds (pBonferroni=4.02×10−10) both identified a significant association to the same region on CFA12. Whole genome sequencing identified a highly expressed FGF4 retrogene within this shared region. The FGF4 retrogene segregated with limb length and had an odds ratio of 51.23 (95% CI = 46.69, 56.20) for IVDD. Long bone length in dogs is a unique example of multiple disease-causing retrocopies of the same parental gene in a mammalian species. FGF signaling abnormalities have been associated with skeletal dysplasia in humans, and our findings present opportunities for both selective elimination of a medically and financially devastating disease in dogs and further understanding of the ever-growing complexity of retrogene biology.



2021 ◽  
pp. 1098612X2110280
Author(s):  
Kayla M Fowler ◽  
Theresa E Pancotto ◽  
Stephen R Werre ◽  
Michaela J Beasley ◽  
William Kay ◽  
...  

Objectives The aim of this study was to evaluate the outcome and prognosis of thoracolumbar feline intervertebral disc disease (IVDD) treated by surgical decompression. Methods This was a multi-institutional retrospective study evaluating the age, breed, sex, body weight, presenting complaint, neuroanatomic diagnosis at presentation, diagnostic imaging results, surgery performed and the overall outcome at discharge and at recheck. Bivariable associations between variables were assessed using the Kruskal–Wallis test (age and grade of IVDD at presentation) and Fisher’s exact test (grade of IVDD at presentation and outcome). Results A total of 35 cats met the inclusion criteria for the study. The most frequently reported clinical sign was difficulty walking (54.2%). The majority of cats presented with an L4–S3 localization (57%). The most common site of intervertebral disc herniation (IVDH) was at L6–L7 (34%). The majority of feline patients that received surgery had a positive outcome at the time of discharge (62.5%; n = 20/32) and at the time of the 2-week recheck (91.3%; n = 21/23). No association was identified between the age of the patient and the grade of IVDD. No association was identified between the presenting grade of IVDD and the clinical outcome at the time of discharge or at the time of recheck evaluation. Conclusions and relevance Cats undergoing spinal decompressive surgery for thoracolumbar IVDH appear to have a favorable prognosis independent of the initial presenting grade of IVDD. A larger sample size and a longer length of follow-up is necessary to obtain statistical associations between the presenting grade of IVDD and overall clinical outcome.



2012 ◽  
Vol 25 (02) ◽  
pp. 109-115 ◽  
Author(s):  
M. Thomas ◽  
J. M. Weh ◽  
J. Bleedorn ◽  
K. Wells ◽  
W. J. Roach

SummaryObjective: To evaluate the presence of residual disc material within the vertebral canal following hemilaminectomy in chondrodystrophic dogs with thoracolumbar intervertebral disc disease.Methods: Forty dogs were treated by hemilaminectomy. Computed tomography was performed preoperatively and immediately postoperatively. The vertebral canal height, width, area, and herniated disc material area were measured. Maximum filling percentage (MFP), residual disc percentage (RDP), maximum residual filling percentage (MRFP), and residual filling percentage (RFP) were calculated. Clinical outcome was determined by telephone interviews.Results: Residual disc material was present in 100% of the dogs. Mean MFP = 55.4% (range 25.9–82.3%; median 56.9%). Mean RDP = 50.3% (range 2.6–155.8%; median 47.9%). Mean MRFP = 30.8% (range 4.9–60%; median 30.1%). Mean RFP = 19.8% (range 4.8–45%; median 19.0%). All dogs were ambulatory with voluntary urination at the long-term follow-up (range: 88–735 days).Clinical significance: Residual disc was present in all dogs following hemilaminectomy for intervertebral disc disease. Residual disc was not associated with failure to achieve functional recovery in these cases.





1971 ◽  
Vol 20 (1) ◽  
pp. 90-94
Author(s):  
M. Naruo ◽  
W. Hoshiko ◽  
E. Koyanagi ◽  
T. Tanaka


1995 ◽  
Vol 129 (3) ◽  
pp. 779-788 ◽  
Author(s):  
R S Slack ◽  
I S Skerjanc ◽  
B Lach ◽  
J Craig ◽  
K Jardine ◽  
...  

The retinoblastoma (RB) protein is present at low levels in early mouse embryos and in pluripotent P19 embryonal carcinoma cells; however, the levels of RB rise dramatically in neuroectoderm formed both in embryos and in differentiating cultures of P19 cells. To investigate the effect of inactivating RB and related proteins p107 and p130, we transfected P19 cells with genes encoding mutated versions of the adenovirus E1A protein that bind RB and related proteins. When these E1A-expressing P19 cells were induced to differentiate into neuroectoderm, there was a striking rise in the expression of c-fos and extensive cell death. The ultrastructural and biochemical characteristics of the dying cells were indicative of apoptosis. The dying cells were those committed to the neural lineages because neurons and astrocytes were lost from differentiating cultures. Cell death was dependent on the ability of the E1A protein to bind RB and related proteins. Our results suggest that proteins of the RB family are essential for the development of the neural lineages and that the absence of functional RB activity triggers apoptosis of differentiating neuroectodermal cells.



Sign in / Sign up

Export Citation Format

Share Document