Drs. Jantine Posthuma de Boer

Treatment of Osteosarcoma Lung Metastases   Osteosarcoma (OS) is the most common primary bone tumour in children and adolescents. It has an incidence of 4/million/year, with a peak incidence at the age of 15-19 years. The tumour generally arises at sites of rapid bone growth, most commonly in the distal femur or proximal tibia. It has a high tendency to systemic spread with >80% of metastasis arising in the lungs. Despite an aggressive treatment regimen, the 5 year survival rate for patients with metastatic disease is 20%. There is a need for new or additional treatment modalities to enhance the current treatment strategy.
In an siRNa screen, I wish to identify proteins that influence the chemosensitivity of OS. In combination experiments I wish to chemo sensitise the OS cells and enhance the efficacy of Doxorubicin. In vitro results will be verified in vivo in a (nude) mouse model for human OS lung metastases which is suited for bioluminescence imaging.
A comparative proteomic study will be conducted on primary osteoblasts and metastasising vs. non-metastasising OS cell lines in order to define tumour-specific and metastasis-specific surface molecules. These molecules can act as a target for targeted delivery of (gene) therapy. Verification of biological behaviour of the cells and targeted delivery of new treatment modalities can also be tested in the mouse model.

Drs. J.L. Bron

Repair of the herniated intervertebral disc                Lumbar discectomy is a well-established surgical procedure to decompress neural structures in patients suffering from a symptomatic herniated lumbar intervertebral disc (IVD). There are, however, serious adverse effects of disc herniation and surgical evacuation on spinal biomechanics. Disc space narrowing may result in discogenic pain or cause overloading in other structures including facet joints, ligaments and muscles by altered motion. The long-term sequelae after discectomy significantly affects the quality of life of the relatively young and employed patient population and therefore has serious socio-economic consequences. In the current project novel treatment strategies, dealing with the damaged  IVD are evaluated. The overall goal of the study is to design and evaluate scaffolds intended for functional replacement of the nucleus pulposus of the IVD. The scaffolds should finally be implanted in a one step surgical procedure in combination with a discectomy and allow invasion by native cells from surrounding tissues. The research includes basic material characterisation (rheology), studying cell-matrix interactions and in vivo evaluation in a goat model. The experiments are performed together with the department of oral cell biology and the FOM Institute for Atomic and Molecular Physics (AMOLF).

Darinka D. Klumpers, MSc

Physical framework in the early development of the vertebral column

Funded by: Research Institute MOVE

In collaboration with: Prof. Mooney lab , Harvard University, Cambridge MA, USA

Regeneration of skeletal tissues is an important focus of the tissue engineering research field. Since we could gain great insight from nature's own process of bone and cartilage formation, valuable information can be attained from embryonic development. My research focuses on the early development of the vertebral column, its patterned structure of alternating bone and cartilage forming an interesting model system. The embryonic development of the vertebral column starts with the formation of a linear pattern of mesenchymal stem cell condensations along the cranial-caudal body axis. While the cell condensations will eventually become the intervertebral discs (cartilage), the non-condensed regions will become the vertebrae (bone). We wonder what initially triggers the mesenchymal stem cells to form clusters, and in particular why these clusters form a regular linear pattern. And subsequently, why do the cells in the condensations differentiate towards cartilage and the non-condensed towards bone?
We hypothesize that generic physical mechanisms form a determining framework in these processes. To address these questions, I am developing a 3D in vitro cell-gel culture model, using mesenchymal stem cells. I'm working on this project in close collaboration with Prof. Mooney's cell and tissue engineering lab at Harvard University, School of Engineering and Applied Sciences .