a comparison of effects of bone marrow stem cell mobilization and bone marrow mesenchymal stem cell transplantation on the recovery of function and regeneration of rat liver tissue after massive excision of liver

Abstract

Objective　To observe the promotion effect of bone mesenchymal stem cells (BMSCs) transplantation and mobilized bone marrow stem cells on the recovery of liver function and liver tissue regeneration after massive partial hepatectomy in rats. Methods　The rats were randomly divided into four groups after massive partial hepatectomy (about 85%), namely massive hepatectomy group (control group, n=15, received massive hepatectomy only), G-CSF group [n=15, received rhG-CSF 150μg/(kg•d) by intraperitoneal injection after the operation for 5 days], MSCs group [n=15, received 5ml suspension of MSCs (about 1.5×106) by tail vein injection after the operation], and G-CSF+MSCs group [n=14, received 1.5ml suspension of MSCs (about 1.5×106) by tail vein injection and rhG-CSF 150μg/(kg•d) by intraperitoneal injection for 5 days after the operation]. The CD34+ cells in the peripheral blood of the rats were assessed by flow cytometry after G-CSF mobilization. Liver function tests including ALT, AST and ALB were performed on the 3rd and 9th day after surgery. All the rats were sacrificed and liver tissue was harvested for histopathological study. The expression of Ki-67 and BrdU positive cells in the liver were determined by immunohistochemistry. Results　Flow cytometric results identified the isolated cells were MSCs. BMSCs in peripheral blood significantly increased in number after rhG-CSF mobilization, and reaching the maximum number on the 5th day. After mobilization for 3, 5 and 9 days, the positive CD34 cells in G-CSF group were 0.009%, 0.016%, 0.019% respectively, which were higher than those in control group. The level of albumin was significantly elevated in three treatment groups compared with control group on the 9th day after the hepatectomy (P<0.05 or P<0.01). The expression of Ki-67 (110.16±27.64, 103.57±33.90, 98.52±21.87 vs 72.39±27.04 cells) and BrdU positive cells (17.96±5.57, 16.45±5.75, 16.66±5.11 vs 11.72±3.83 cells) in three treatment groups were higher than those in control group, with a statistically significant difference (P<0.01). Conclusion　Mobilization of hematopoietic stem cells by G-CSF or transplantation of allogenic BMSCs can promote the recovery of liver function and liver tissue regeneration, but their combination fails to show a synergistic effect. DOI: 10.11855/j.issn.0577-7402.2014.08.01