title: Evaluation of the effects of preconditioning regimens on hepatic veno-occlusive disease in mice after hematopoietic stem cell transplantation.
abstract: 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.
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou 221002, China; Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China; Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Qiao
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou 221002, China; Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China.
authors.forename: Jinyu
authors.initials: J
authors.lastname: Fu
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou 221002, China; Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Fang
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou 221002, China; Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China.
authors.forename: Yujin
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou 221002, China; Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China.
authors.forename: Hongling
authors.initials: H
authors.lastname: Mi
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou 221002, China; Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China.
authors.forename: Na
authors.initials: N
authors.lastname: Yang
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou 221002, China; Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou 221002, China; Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China; Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China. Electronic address: lihmd@163.com.
authors.forename: Kailin
authors.initials: K
authors.lastname: Xu
authors.affiliation: Blood Diseases Institute, Xuzhou Medical College, Xuzhou 221002, China; Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou 221002, China; Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China. Electronic address: zengly2000@163.com.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Zeng
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000633:toxicity*; D017209:Apoptosis; D001792:Blood Platelets / Q000187:drug effects / Q000528:radiation effects; D002066:Busulfan / Q000008:administration & dosage; D049109:Cell Proliferation; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000008:administration & dosage; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D005337:Fibrin / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006504:Hepatic Veno-Occlusive Disease / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D015994:Incidence; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008933:Mitochondrial Swelling / Q000187:drug effects / Q000528:radiation effects; D015539:Platelet Activation / Q000187:drug effects / Q000528:radiation effects; D012156:Reticulocytes / Q000187:drug effects / Q000528:radiation effects; D019172:Transplantation Conditioning / Q000009:adverse effects*; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation / Q000009:adverse effects*
chemical_list: D003520:Cyclophosphamide; D005337:Fibrin; D002066:Busulfan
keywords: Busulfan; Cyclophosphamide; Hematopoietic stem cell transplantation; Hepatic veno-occlusive disease; Total body irradiation