Project B1

Aim of project B1 is 1) to gain broader insights into the pathogenesis of myeloma bone disease as basis for further development of bone substitute materials. 2) Identification of patients (together with B8, B9) who will benefit from a therapy using such materials regarding a local control of the myeloma cell population and treatment of the bone defect. 3) In vitro testing of developed materials on myeloma cell lines and primary myeloma cells, as well as definition of the direction of development (particularly regarding the release of compounds, e.g. bortezomib/carfilzomib, BMP-6). 4) Transfer and extension of the material concept on non-malignant diseases (e.g. osteoporotic fractures).

Figure 1. Myeloma bone disease. A. Physiological situation with coupled osteoblastic bone formation (blue) und osteoclastic bone resorption (red). B. Initially in multiple myeloma, there is an increased bone resorption with bone formation keeping step (intact „bone remodeling compartments“). C. Bone remodeling compartments are disrupted by the interaction with myeloma cells (violet) leading to increased bone resorption while bone formation has been almost fully suspended.

Thereby, bone defects increasingly come into the focus of our attention as i) they represent a serious and because of prolonged survival times still an unsolved clinical problem and ii) are osteolytic lesions (focal lesions) a potential niche for residual myeloma cells and therefore the potential origin for a clinical relapse.

Aim of this sub-project is the investigation of three essential, complementary issues regarding bone destruction in multiple myeloma:

1. Increased understanding of the pathogenesis of bone destruction in multiple myeloma laying the basis for the development of appropriate bioactive bone substitutes (stabilization, prevention of a proliferative stimulus to myeloma cells, additional local control of the malignant cell population).
2. In vitro tests of the bone substitutes that are developed by sub-projects M1-M4 and their appropriate modifications (M5-M7) on human myeloma cell lines as well as primary myeloma cells and definition of the direction of development. 
3. Transfer of the generated results on other benign and malign disease entities (myeloma as model disease).

Principle Investigators (PI)
Dr. med. Dipl. phys. Dirk Hose Laborleiter des Labors für Myelomforschung Medizinische Klinik V Universitätsklinikum Heidelberg und Nationales Centrum für Tumorerkrankungen Heidelberg Contact: Im Neuenheimer Feld 410 69120 Heidelberg Telefon: +49 (0)6221 / 56 39 047 E-Mail: dirk.hose@med.uni-heidelberg.de
Prof. Dr. med. Hartmut Goldschmidt Leiter der Sektion Multiples Myelom Medizinische Klinik V Universitätsklinikum Heidelberg und Nationales Centrum für Tumorerkrankungen Heidelberg Contact: Im Neuenheimer Feld 410 69120 Heidelberg Telefon: +49 (0)6221 / 56 80 03 Fax: +49 (0)6221 / 56 56 47 E-Mail: hartmut.goldschmidt@med.uni-heidelberg.de
Co-Workers
Dr. med. Anja Seckinger Wissenschaftliche Mitarbeiterin Labor für Myelomforschung Medizinische Klinik V Universitätsklinikum Heidelberg und Nationales Centrum für Tumorerkrankungen Heidelberg Anschrift: Im Neuenheimer Feld 410 69120 Heidelberg E-Mail: anja.seckinger@med.uni-heidelberg.de
Dipl. bioinf. (FH) Tobias Meißner Bioinformatiker Labor für Myelomforschung Medizinische Klinik V Universitätsklinikum Heidelberg und Nationales Centrum für Tumorerkrankungen Heidelberg Contact: Im Neuenheimer Feld 410 69120 Heidelberg E-Mail: tobias.meissner@med.uni-heidelberg.de
Katrin Heimlich Medizinisch-Technische Assistentin Labor für Myelomforschung Medizinische Klinik V Universitätsklinikum Heidelberg und Nationales Centrum für Tumorerkrankungen Heidelberg Contact: Im Neuenheimer Feld 410 69120 Heidelberg E-Mail: katrin.heimlich@med.uni-heidelberg.de