Multiple Myeloma (Kahler’s Disease): new therapies in novel animal models
Thursday 16 April 2009
Project
The Multiple Myeloma (MM), or Kahler's disease is a cancer of the white blood cells known as plasma cells and it occurs in the bone marrow. Myeloma is difficult to cure, but treatment with chemotherapy or stem cell transplants can prolong the life span of patients. Our research is focused on studying the pathology of this disease in novel humanized mouse models and on preclinical development of new therapies to treat this disease. The human MM cell lines that we study in these mice are genetically marked with the Firefly luciferase gene (Fluc) so that we can use molecular imaging technology, based on bioluminescence and fluorescence in live animals to detect tumors growing in various locations, but primarily in the bone marrow of the mouse and to monitor the effect of treatment given.
We recently improved our mouse myeloma model by creating a humanized in vivo model in the RAG2γc KO mouse. A key feature is the creation of human bone in subcutaneously placed scaffolds seeded with bone marrow (BM)-derived mesenchymal stem cells. We showed that the vascularized ossicles formed in these scaffolds contain human bone, hereby providing a 3-D natural “niche” for MM cell growth. When patient derived myeloma cells are injected into these ossicles we indeed observe outgrowth of human myeloma cells connected to the bony layer and with bone lesions, resembling clinical MM. This provides us with an optimal platform to study pathogenesis of MM and to use the model for preclinical drug testing.
Techniques
Cell culture, FACS analysis/sorting, viral gene marking, molecular imaging (BLI-Fluor) in animal experiments (optional), luciferase assay, liposome production, MSC expansion/differentiation, immuno-histochemistry
Duration
6 or 9 months
Contact
Dr Anton Martens, a.martens@umcutrecht.nl, 088 75 540 09
Dr Kristin Denzer, k.denzer@umcutrecht.nl, 088 75 576 73
More info
UMC Utrecht - dept. of Immunology
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