STEM CELL GENE THERAPY
The working group conducts basic and preclinical research in the areas of: gene therapy, stem cell biology/therapy, hematopoietic growth factor therapy development, and radiation biology/protection. The group has a tradition of international collaborative research and the project leader a longstanding record of coordinating projects of the European Research Framework Programs.
 
Gene Therapy
The translational gene therapy research is directed at implementation of novel therapies using genetically repaired hematopoietic stem cells, with focus on the treatment of monogenic immune deficiencies and storage disorders, and gene therapy for hemoglobin disorders as a more future research aim. To this end, the working group is involved in the development of lentiviral vectors for genetic modification of hematopoietic stem cells with curative intent, evaluation of efficacy and safety in disease specific mouse models and nonhuman primates, with presently emphasis on the analysis of insertional mutagenesis and leukemogenesis and on molecular mechanisms involved in the repopulation capacity of stem cells.
Websites: www.gene-therapy.eu, www.magselectofection.eu

Stem Cell Biology & Therapy
Experimental stem cell transplantation is focused on identification and characterization of stem cell subsets with the capacity of short- and long-term reconstitution following transplantation, manipulation of such cells, stem cell graft engineering and in vivo and in vitro expansion of stem cells, including identification of the stem cell receptor distribution. In addition to other murine models for inherited diseases, the prime model used is transplantation of male BALB/c donor stem cells into female BALB/c a-thalassemic recipients. Other available models include the NOD-SCID and Rag1-/gamma-c- recipient mouse models for human stem cells. Much of the stem cell biology research is currently integrated into the gene therapy topic, with lentiviral marking of stem cells as a major tool to study stem cell reconstitution and clonality issues relevant for both gene therapy and radiation protection aims of the research.

Hematopoietic Growth Factor Treatment development
Using the bone marrow transplantation and radiation induced myelosuppression models in nonhuman primates, preclinical studies are focused on growth factors that promote the reconstitution of immature hematopoietic stem cells, and are supplemented with mechanistic studies in mice. Recently, preclinical studies were completed on the mechanisms of action, efficacy and safety of thrombopoietin in synergy with other growth factor and androgenic steroid treatment.

Radiation Biology & Protection
Whole body exposure occurs in - rare - radiation accidents and in therapeutic settings, especially for bone marrow transplant recipients. The research activities focus on stem cell radiation protection and include studies on growth factor prevention of apoptosis of stem cells and mechanisms that promote hematopoietic reconstitution. The radiation biology research for the accident situation involves evaluation of the health consequences of radiation accidents, the development of diagnosis and treatment protocols, and generic research on hematopoietic growth factor therapy, recently extended to signaling pathways controlling the reconstitution capacity of stem cells.