Mesenchymal stromal cells (MSCs) support hematopoiesis in the bone marrow, are involved in tissue repair and modulate immune responses. The aim of this thesis is to study the function of MSC... Show moreMesenchymal stromal cells (MSCs) support hematopoiesis in the bone marrow, are involved in tissue repair and modulate immune responses. The aim of this thesis is to study the function of MSC derived from children suffering from childhood malignant diseases (Myelodysplastic syndrome (MDS) and Juvenile myelomonocytic leukemia (JMML)) or from systemic juvenile idiopathic arthritis. The MSCs form children with MDS and JMML have an altered RNA expression profile with marked differences in e.g. immunomodulatory genes. These alterations were reversible after hematopoietic stem cell transplantation (HSCT). Our data support the hypothesis that malignant cells profit from the altered bone-marrow microenvironment by escaping the immune defense and occupying the hematopoietic niche. In the future, these mechanisms will be possible targets for therapy. In addition, the impact of MSCs on virus-specific immune recovery and acute graft-versus-host disease (aGvHD) after pediatric allogeneic HSCT has been investigated. We show in the studies described that biopsies of the intestinal tract are essential at diagnosis but also to monitor treatment after experimental therapy. Our data support early treatment with MSCs in steroid refractory aGvHD irrespective of ongoing viral reactivations. These data were used for the design of a multi-center randomized controlled trial with MSCs. Show less
