title: A murine model of hepatic veno-occlusive disease induced by allogeneic hematopoietic stem cell transplantation.
abstract: Hepatic veno-occlusive disease (HVOD) is a life-threatening complication of bone marrow stem cell transplantation. The understanding of this clinical condition is hampered by the lack of suitable animal models. Here, we present a murine (BALB/c-based) model of HVOD induced by allogeneic hematopoietic stem cell transplantation (allo-HSCT). The chimerism rate of bone marrow was measured on days 5 and 10, while the chimerism rate of peripheral blood was measured on day 15 after allo-HSCT. Percentages of peripheral reticulocytes and serum levels of bilirubin and alanine aminotransferase (as liver function tests) were measured on days 5, 10, 15, 20, and 30. Livers were obtained on days 5, 10, 15, 20, and 30, and fixed in formaldehyde or glutaric dialdehyde. Liver slices were processed using the hematoxylin-eosin, Masson's trichrome, or immunohistochemistry staining, and examined by light or transmission electron microscopy. Sinusoidal damages were the earliest pathological changes occurring in the allo-HSCT-induced HVOD, followed by coagulative necrosis of liver cells. The liver cell necrosis was later attenuated and sinusoidal endothelial cell morphology improved. However, on day 30, the edema and necrosis of liver cells became aggravated again. Furthermore, sinusoidal lining cell regeneration and partly attenuated liver cell necrosis were followed by the moderate to severe central vein fibrosis. In conclusion, we have successfully established a murine model of HSCT-HVOD. This model develops moderate to severe HVOD which cannot heal without intervention.
authors.affiliation: Nanjing General Hospital of Nanjing Military Command, No. 305 East Zhongshan Road, Nanjing, 210002, China, zengly2000@163.com.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Zeng
authors.forename: Licai
authors.initials: L
authors.lastname: An
authors.forename: Ting
authors.initials: T
authors.lastname: Fang
authors.forename: Bin
authors.initials: B
authors.lastname: Pan
authors.forename: Haiying
authors.initials: H
authors.lastname: Sun
authors.forename: Chong
authors.initials: C
authors.lastname: Chen
authors.forename: Jiang
authors.initials: J
authors.lastname: Cao
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
authors.forename: Kailin
authors.initials: K
authors.lastname: Xu
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001663:Bilirubin / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006504:Hepatic Veno-Occlusive Disease / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009336:Necrosis / Q000209:etiology; D014184:Transplantation, Homologous
chemical_list: D016207:Cytokines; D000410:Alanine Transaminase; D001663:Bilirubin