Evaluation of the effects of preconditioning regimens on hepatic veno-occlusive disease in mice after hematopoietic stem cell transplantation.
Pre-conditioning regimens before hematopoietic stem cell transplantation (HSCT), such as total body irradiation (TBI) or busulfan/cyclophosphamide (BU/CY), are associated with hepatic veno-occlusive disease (HVOD). However, the mechanism of these regimens on hepatic veno-occlusive disease remains unclear. The aim of this study is to evaluate the effect of TBI or BU/CY on HVOD in mice after HSCT. Mice received TBI or BU/CY followed by HSCT. Analysis of liver pathology and function, and platelet aggregation were performed. Both these regimens caused damage to liver sinusoid endothelial cells, leading to loss of normal structural integrity of liver sinusoid, abnormal liver function, fibrin deposition, inflammatory cells infiltration and platelet aggregation. No differences of liver function in these regimens were observed. Increased hepatic lipid droplets, mitochondrial swelling and higher incidence of HVOD were observed in BU/CY. In conclusion, both TBI and BU/CY caused damage to liver sinusoid endothelial cells and occurrence of HVOD with higher incidence for BU/CY. Meanwhile, inflammation and platelet activation was also observed, suggesting targeting them maybe beneficial in the prophylaxis of HVOD.
['Qiao|Jianlin|J|', 'Fu|Jinyu|J|', 'Fang|Ting|T|', 'Huang|Yujin|Y|', 'Mi|Hongling|H|', 'Yang|Na|N|', 'Chen|Chao|C|', 'Xu|Kailin|K|', 'Zeng|Lingyu|L|']
D000818:Animals D000971:Antineoplastic Combined Chemotherapy Protocols D017209:Apoptosis D001792:Blood Platelets D002066:Busulfan D049109:Cell Proliferation D002478:Cells, Cultured D003520:Cyclophosphamide D004730:Endothelium, Vascular D005260:Female D005337:Fibrin D018380:Hematopoietic Stem Cell Transplantation D006504:Hepatic Veno-Occlusive Disease D006801:Humans D007124:Immunoenzyme Techniques D015994:Incidence D008099:Liver D008297:Male D051379:Mice D008807:Mice, Inbred BALB C D008810:Mice, Inbred C57BL D008933:Mitochondrial Swelling D015539:Platelet Activation D012156:Reticulocytes D019172:Transplantation Conditioning D014184:Transplantation, Homologous D014916:Whole-Body Irradiation
Hepatic veno-occlusive disease Hematopoietic stem cell transplantation Total body irradiation Busulfan Cyclophosphamide