In vitro analysis of osteogenic inhibition in non-union spinal fusion caused by nucleus pulposus cells.

Tekari, Adel; Chan, Samantha; Frauchiger, Daniela Angelika; Benneker, Lorin Michael; Heini, Paul Ferdinand; Gantenbein, Benjamin (29 June 2015). In vitro analysis of osteogenic inhibition in non-union spinal fusion caused by nucleus pulposus cells. In: 11th Swiss Stem Cell Network Annual Meeting. 29.06.2015.

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-arthrosis. 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 osseo-induction of bone marrow-derived mesenchymal stem cells (MSC) by antagonizing BMP-inhibitors. 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. MSCs were kept in 1:control medium, 2:osteogenic medium±alginate beads, 3:osteogenic medium+NPC (±L51P) and 4:osteogenic medium+AFC (±L51P) for 21 days. Relative gene expression of bone-related genes, alkaline phosphatase assay and histological staining were performed. 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 L51Pto the co- cultures, however, induced mineralization of MSCs in presence of NPC. 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 (Poster)

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 16:25

Last Modified:

26 Jan 2016 16:25

URI:

https://boris.unibe.ch/id/eprint/75386

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