Investigation of bone inhibition in non-union spinal fusion caused by intervertebral disc cells in vitro

Tekari, Adel; Chan, Samantha; Frauchiger, Daniela Angelika; Benneker, Lorin Michael; Heini, Paul Ferdinand; Gantenbein, Benjamin (21 May 2015). Investigation of bone inhibition in non-union spinal fusion caused by intervertebral disc cells in vitro (Unpublished). In: Annual Meeting of the SVGO/SBMS (Swiss Bone Mineral Society).

Introduction: Discectomy and spinal fusion is the gold standard for spinal surgery to relieve pain. However, fusion can be hindered for yet unknown reasons that lead to non-fusions with pseudo-arthrose. It is hence appealing to develop biomaterials that can enhance bone formation. Clinical observations indicate that presence of residual intervertebral disc (IVD) tissue might hinder the ossification. We hypothesize that BMP-antagonists are constantly secreted by IVD cells and potentially prevent the ossification process. Furthermore, L51P, the engineered BMP2 variant, stimulates osteoinduction of bone marrow-derived mesenchymal stem cells (MSC) by antagonizing BMP-inhibitors. Methods: Human MSCs, primary nucleus pulposus (NPC) and annulus pulposus cells (AFC) were isolated and expanded in monolayer cultures up to passage 3. IVD cells were seeded in 1.2% alginate beads (4Mio/mL) and separated by culture inserts from MSCs in a co-culture set-up. MSCs were kept in 1:control medium, 2:osteogenic medium+alginate control, 3:osteogenic medium+NPC (±L51P) and 4:osteogenic medium+AFC (±L51P) for 21 days. Relative gene expression of bone-related genes, Alkaline Phosphatase (ALP) assay and histological staining were performed. Results: Osteogenesis of MSCs was hindered as shown by reduced alizarin red staining in the presence of NPC. No such inhibition was observed if co-cultured with alginate only or in the presence of AFC. The results were confirmed on the RNA and protein level. Addition of L51P to the co-cultures induced mineralization of MSCs, however a reduced ALP was observed. Conclusion: We demonstrated that NPC secrete BMP-antagonists that prevent osteogenesis of MSCs and L51P can antagonize BMP-antagonists and induce bone formation.

Item Type:

Conference or Workshop Item (Speech)

Division/Institute:

04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Orthopaedic Surgery
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute for Surgical Technology & Biomechanics ISTB

UniBE Contributor:

Tekari, Adel; Chan, Samantha; Frauchiger, Daniela Angelika; Benneker, Lorin Michael; Heini, Paul Ferdinand and Gantenbein, Benjamin

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

Language:

English

Submitter:

Adel Tekari

Date Deposited:

26 Jan 2016 17:03

Last Modified:

01 Feb 2016 08:56

URI:

https://boris.unibe.ch/id/eprint/75388

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