Bone-marrow derived cells participate in extramedullary hematopoiesis in a model of acetaminophen-induced acute liver failure in rats


Adult derived mononuclear bone marrow cells are a good alternative as cell therapy. These cells are capable of significantly improve survival rate of Wistar rats with acetaminophen (APAP) induced acute liver failure in ten days. However, long term of cell therapy is not deeply studied in the literature. Here, we report an extramedullary hematopoiesis process derived from transplanted mononuclear bone marrow cells in the liver of rats 10 days after APAP injection. This result indicates that liver maintains an adequate microenvironment for the occurrence of extramedullary hematopoiesis process. The consequence of this finding deserves more studies.

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Cristina Belardinelli, M. , López, M. , Giacomet de Carvalho, T. , Mayer, F. , Baldo, G. , Meurer, L. , Giugliani, R. and Matte, U. (2013) Bone-marrow derived cells participate in extramedullary hematopoiesis in a model of acetaminophen-induced acute liver failure in rats. Stem Cell Discovery, 3, 44-46. doi: 10.4236/scd.2013.31007.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Polson, J. and Lee, W.M. (2005) AASLD position paper: The management of acute liver failure. Hepatology, 41, 1179-1197. doi:10.1002/hep.20703
[2] Lee, W.M., Squires, R.H., Nyberg, S.L., Doo, E. and Hoofnagle, J.H. (2008) Acute liver failure: Summary of a workshop. Hepatology, 47, 1401-1415. doi:10.1002/hep.22177
[3] Mcgill, M.R., Sharpe, M.R., Williams, C.D., Taha, M., Curry, S.C. and Jaeschke, H. (2012) The mechanism underlying acetaminophen-induced hepatotoxicity in humans and mice involves mitochondrial damage and nuclear DNA fragmentation. The Journal of Clinical Investigation, 122, 1574-1583. doi:10.1172/JCI59755
[4] Nelson, S. (1990) Molecular mechanisms of the hepatotoxicity caused by acetaminophen. Seminars in Liver Disease, 10, 267-278. doi:10.1055/s-2008-1040482
[5] Gujral, J., Knight, T., Farhood, A., Bajt, M. and Jaeschke H. (2000) Mode of cell death after acetaminophen overdose in mice: apoptosis or oncotic necrosis? Toxicological Sciences: An official journal of Society of Toxicology, 67, 322-328.
[6] Baldo, G, Giugliani, R., Uribe, C., Belardinelli, M.C., Duarte, M.E.S., Meurer, L., da Silveira, T.R. and Matte U. (2010) Bone marrow mononuclear cell transplantation improves survival and induces hepatocyte proliferation in rats after CCl(4) acute liver damage. Digestive diseases and sciences, 55, 3384-3392. doi:10.1007/s10620-010-1195-4
[7] Li, J., Zhang, L., Xin, J., Jiang, L., Zhang, T., Jin, L., Li, J., Zhou, P., Hao, S., Cao, H. and Li L. (2012) Immediate intraportal transplantation of human bone marrow mesenchymal stem cells prevents death from fulminant hepatic failure in pigs. Hepatology, 56, 2-38. doi:10.1002/hep.25722
[8] Belardinelli, M.C., Pereira, F., Baldo, G., Vicente Tavares, A.M., Kieling, C.O., da Silveira, T.R., Meurer, L., Soares Duarte, M.E., Giugliani, R. and Matte, U. (2008) Adult derived mononuclear bone marrow cells improve survival in a model of acetaminophen-induced acute liver failure in rats. Toxicology, 247, 1-5. doi:10.1016/j.tox.2008.01.015
[9] Sant’anna, N.I., Kalil, R.A., Pretto Neto, A.S., Pivatto Júnior, F., Fracasso, J., Sant’anna, J.R., Marques, M., Markoski, M., Prates, P.R. and Nardi, N.B. (2010) Global contractility increment in nonischemic dilated cardiomyopathy after free wall-only intramyocardial injection of autologous bone marrow mononuclear cells: An insight over stem cells clinical mechanism of action. Cell Transplantation, 19, 959-964. doi:10.3727/096368910X514648
[10] Coura, R., Prolla, J., Meurer, L. and Ashton-Prolla, P. (2005) An alternative protocol for DNA extraction from formalin fixed and paraffin wax embedded tissue. Journal of Clinical Pathology, 58, 894-895. doi:10.1136/jcp.2004.021352
[11] Otsuka, H., Yagi, H., Endo, Y., Nonaka, N. and Nakamura, M. (2011) Kupffer cells support extramedullary erythropoiesis induced by nitrogen-containing bisphosphonate in splenectomized mice. Cellular Immunology, 271, 197-204. doi:10.1016/j.cellimm.2011.06.025
[12] Gürsoy, M., Haznedaro?lu, I.C., Celik, I., Sayinalp, N., Ozcebe, O.I. (1996) Agranulocytosis, plasmacytosis, and thrombocytosis followed by a leukemoid reaction due to acute acetaminophen toxicity. The Annals of Pharmacotherapy, 30, 762-765.
[13] MacKinnon, H. and Menon, R. (1974) Letter: Reaction to acetaminophen. Canadian Medical Associacion Journal, 8, 1237-1239.
[14] Datta, S. (1973) Fatal pancytopenia after administration of fortagestic. British Medical Journal, 21,173. doi:10.1136/bmj.3.5872.173-c
[15] Lister, C. and McLean, A. (1997) Inhibition of DNA synthesis by paracetamol in different tissues of the rat in vivo. Toxicology, 15, 49-57. doi:10.1016/S0300-483X(96)03521-4
[16] Michalopoulos, G.K. (2007) Liver regeneration. Journal of Cell Physiology, 213, 286-300. doi:10.1002/jcp.21172
[17] Bodo, M., Baroni, T. and Tabilio, A. (2009) Haematopoietic and stromal stem cell regulation by extracellular matrix components and growth factors. Journal of Stem Cells, 4, 57-69.
[18] Mendt, M. and Cardier, J.E. (2012) Stromal-derived factor-1 and its receptor, cxcr4, are constitutively expressed by mouse liver sinusoidal endothelial cells: Implications for the regulation of hematopoietic cell migration to the liver during extramedullary hematopoiesis. Stem Cells and Development, 21, 2142-2151. doi:10.1089/scd.2011.0565
[19] Cardier, J.E. and Barberá-Guillem, E. (1997) Extramedullary hematopoiesis in the adult mouse liver is associated with specific hepatic sinusoidal endothelial cells. Hepatology, 26, 165-175. doi:10.1002/hep.510260122

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