Transplantation of bone marrow cells decreases tumor necrosis factor-α production and blood-brain barrier permeability and improves survival in a mouse model of acetaminophen-induced acute liver disease

dc.creatorSouza, Bruno Solano de Freitas
dc.creatorNascimento, Ramon Campos
dc.creatorOliveira, Sheilla Andrade de
dc.creatorVasconcelos, Juliana Fraga
dc.creatorKaneto, Carla Martins
dc.creatorCarvalho, Lian Felipe Paiva Pontes de
dc.creatorSantos, Ricardo Ribeiro dos
dc.creatorSoares, Milena Botelho Pereira
dc.creatorFreitas, Luiz Antonio Rodrigues de
dc.date2014-04-24T13:36:22Z
dc.date2014-04-24T13:36:22Z
dc.date2012
dc.date.accessioned2023-09-27T00:07:14Z
dc.date.available2023-09-27T00:07:14Z
dc.identifierSOUZA, B. S. de F. et al. Transplantation of bone marrow cells decreases tumor necrosis factor-α production and blood-brain barrier permeability and improves survival in a mouse model of acetaminophen-induced acute liver disease. Cytotherapy, v. 14, n. 8, p. 1011-1021, 2012.
dc.identifier1465-3249
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/7533
dc.identifier10.3109/14653249.2012.684445
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8897635
dc.descriptionBackground aims. Acute liver failure (ALF), although rare, remains a rapidly progressive and frequently fatal condition. Acetaminophen (APAP) poisoning induces a massive hepatic necrosis and often leads to death as a result of cerebral edema. Cell-based therapies are currently being investigated for liver injuries. We evaluated the therapeutic potential of transplantation of bone marrow mononuclear cells (BMC) in a mouse model of acute liver injury. Methods. ALF was induced in C57Bl/6 mice submitted to an alcoholic diet followed by fasting and injection of APAP. Mice were transplanted with 107 BMC obtained from enhanced green fluorescent protein (GFP) transgenic mice. Results. BMC transplantation caused a significant reduction in APAP-induced mortality. However, no significant differences in serum aminotransferase concentrations, extension of liver necrosis, number of inflammatory cells and levels of cytokines in the liver were found when BMC- and saline-injected groups were compared. Moreover, recruitment of transplanted cells to the liver was very low and no donor-derived hepatocytes were observed. Mice submitted to BMC therapy had some protection against disruption of the blood-brain barrier, despite their hyperammonemia, and serum metalloproteinase (MMP)-9 activity similar to the saline-injected group. Tumor necrosis factor (TNF)-α concentrations were decreased in the serum of BMC-treated mice. This reduction was associated with an early increase in interleukin (IL)-10 mRNA expression in the spleen and bone marrow after BMC treatment. Conclusions. BMC transplantation protects mice submitted to high doses of APAP and is a potential candidate for ALF treatment, probably via an immunomodulatory effect on TNF-α production.
dc.formatapplication/pdf
dc.languageeng
dc.publisherTaylor & Francis
dc.rightsrestricted access
dc.subjectAcetaminophen
dc.subjectAcute liver failure
dc.subjectBone marrow mononuclear cells
dc.subjectBrain edema
dc.subjectCell therapy
dc.subjectTumor necrosis factor
dc.titleTransplantation of bone marrow cells decreases tumor necrosis factor-α production and blood-brain barrier permeability and improves survival in a mouse model of acetaminophen-induced acute liver disease
dc.typeArticle


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