gms | German Medical Science

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2015)

20.10. - 23.10.2015, Berlin

Stem cell effect is influenced by the degenerative state of intervertebral discs

Meeting Abstract

  • Marianna Peroglio - AO Research Institute Davos, Davos, Switzerland
  • Stephanie Caprez - AO Research Institute Davos, Davos, Switzerland
  • Lorin Michael Benneker - Department of Orthopaedic Surgery, University of Berne, Bern, Switzerland
  • Mauro Alini - AO Research Institute Davos, Davos, Switzerland
  • presenting/speaker Sibylle Grad - AO Research Institute Davos, Davos, Switzerland

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2015). Berlin, 20.-23.10.2015. Düsseldorf: German Medical Science GMS Publishing House; 2015. DocGR18-1091

doi: 10.3205/15dkou501, urn:nbn:de:0183-15dkou5016

Veröffentlicht: 5. Oktober 2015

© 2015 Peroglio et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Objectives: The use of mesenchymal stem cell (MSC) for the treatment of degenerative disc disease has been described in the literature. It has been suggested that MSCs could differentiate into disc-like cells or could release trophic factors that stimulate the resident disc cells in response to the disc environment. Our hypothesis was that the regenerative response induced by therapeutic MSCs would be conditioned by the degenerative state of intervertebral discs (IVDs).

Methods: Disc degeneration was induced by high-frequency loading (7 days of loading, 3 hours/day, maximum strain = 10% of disc height, 10 Hz) on bovine caudal IVDs (n=40, 4-10 months). Control discs included IVDs loaded at a physiological frequency (0.1 Hz) and unloaded IVDs. Following this treatment, IVDs were nucleotomised by incision through the endplate and filled with either human bone marrow derived MSCs in fibrin, fibrin only, human MSCs in saline solution, or saline solution only. Discs were loaded physiologically for additional 7 days. Outcome parameters included disc height (DH), cell viability, gene expression and histology. After confirming the equal variance and normal distribution, data were statistically analysed by One-way ANOVA and Bonferroni post-hoc for each time point. When only two groups were compared, an independent t-test was used (p<0.05).

Results and Conclusion: High-frequency degenerative loading induced a significantly higher DH loss than physiological conditions (-8.7±2.0% and -3.5±4.8%, respectively) and a stronger type I collagen (COL1), type II collagen (COL2) and aggrecan (ACAN) down-regulation. Fibrin supplementation (with or without MSCs) induced a significantly higher DH recovery after free swelling (5.3±3.4% relative to initial DH) compared to saline solution (0.8±3.5%). MSC viability inside the IVD was maintained (>90% after one week). Gene expression analyses indicated that physiologically loaded disc cells responded better to the MSC treatment than degenerative disc cells, as attested by the up-regulation of the anabolic markers COL1 and COL2 in all tissues collected from physiologically loaded discs. ACAN expression was more sensitive to loading changes than to MSC supplementation, which suggests that IVD cells have a recovery capacity from injurious loading, at least if the latter is applied for a limited period of time. Interestingly, the presence of MSCs had no effect on the expression of ACAN, MMP3 or ADAMTS4 in disc tissue. The degenerative state of the IVDs also influenced the differentiation of the implanted MSCs. Indeed, degenerative-loaded discs induced a significantly stronger up-regulation of KRT19 and CD24 but a lower up-regulation of CA12 than physiologically loaded discs. In conclusion, stem cells may contribute to the restoration of degenerated discs by inducing an up-regulation of anabolic markers in the disc cells. However, both MSC and IVD cell responses depend on the disc degeneration state, which needs to be considered in the development of stem cell-based therapies.