Abstract
IntroductionOn the basis of the recently recognized potential of hematopoietic stem cells (HSCs) to give rise to hepatocytes, we have assessed the potential of granulocyte colony-stimulating factor (G-CSF)-mobilized bone marrow-derived CD34+ HSCs to contribute to faster recovery and promote regeneration process after acute liver injury by radiation.MethodsG-CSF-mobilized CD34+ HSCs (1 × 105 cells per mouse) were injected via tail vein in the irradiated femal nonobese diabetic/severe combined immunodeficient mice. Irradiated control animals received only saline infusion.ResultsThe mobilized CD34+ HSCs significantly ameliorated radiation-induced liver damage. In the liver of recipient mice killed 21 days after irradiation, human albumin+ Y-chromosome+ hepatocyte-like cells, or human cytokeratin+ Y-chromosome+ hepatocyte-like cells formed cords of hepatocytes, occupied ~30% of the 4-μm section surrounding portal tracts. Furthermore, human-specific albumin mRNA expressed in the liver and human albumin was detected in the serum only in the CD34+ HSC-treated mice.ConclusionsTreatment with G-CSF-mobilized CD34+ HSCs from bone marrow into peripheral blood could significantly promote tissue reparation after acute liver injury by radiation in mice, possibly by the ability of CD34+ HSCs to generate hepatocytes. So mobilization of CD34+ HSCs might offer a novel therapeutic approach for the treatment of radiation-induced complications after radiotherapy or other acute liver diseases in humans.
Highlights
On the basis of the recently recognized potential of hematopoietic stem cells (HSCs) to give rise to hepatocytes, we have assessed the potential of granulocyte colony-stimulating factor (G-CSF)-mobilized bone marrow-derived CD34+ HSCs to contribute to faster recovery and promote regeneration process after acute liver injury by radiation
G-CSF-mobilized CD34+ HSCs ameliorate radiationinduced liver injury The initial challenge to study G-CSF-mobilized CD34+ cells to hepatocyte differentiation was to establish a model of acute liver damage in immunodeficient mice, in which the control mice that did not undergo transplantation would recover from the injury
In Group 1 (G1) and Group 2 (G2) mice, the activity of serum alanine aminotransferase aspartate (ALT) and AST showed initially significantly elevated and gradually decreased with time, and in the G1 mice, both ALT and AST presented significantly lower values when compared with the values found in G2 mice at the same time points (Table 1)
Summary
On the basis of the recently recognized potential of hematopoietic stem cells (HSCs) to give rise to hepatocytes, we have assessed the potential of granulocyte colony-stimulating factor (G-CSF)-mobilized bone marrow-derived CD34+ HSCs to contribute to faster recovery and promote regeneration process after acute liver injury by radiation. The most important dose-limiting factor is sensitivity of the normal tissue lying in the radiation field. Even with the most optimal radiation schedule, damage still occurs in normal tissues. Radiotherapy has played a limited role in the treatment of malignant intrahepatic cancers owing to the low tolerance of liver to radiotherapy. Radiationinduced liver damage had been observed in 5-10% of patients, who had received radiation doses exceeding 30 Gy [1,2].
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