Pathophysiological Aspects of Transplantation-related Complications:: Following Busulphan / Cyclophosphamide Conditioning Regimen in Mouse Model

Our stem cell transplantation mouse model following busulfan-cyclophosphamide (Bu-Cy) conditioning is a reliable model for studying several factors that are involved in the development of graft versus host disease after chemotherapy. It is also a useful model for evaluating different agents in the treatment of GVHD. All studies in this thesis utilized this model. Naïve T cells undergo early allo-activation by host/donor APCs in the secondary lymphoid organs to produce effector/memory T cells that initiate tissue damage in GVHD. Decreased spleen cellularity and diminished glycogen content in the liver were observed after conditioning regimen. No morphological changes were observed in kidney in either HSCT setting. Histopathological changes such as vasculitis, inflammation and apoptotic cell forms in liver, spleen, pancreas, lungs and heart were observed in allogeneic transplanted mice, however, only hypocellular spleen and extramedullar hematopoiesis were detected in syngeneic transplanted animals. Short term consequences of Bu-Cy treatment divergently affect large and small arteries of the cardiovascular system.