Protective effects of bone marrow mesenchymal stem cells transplantation Combined with bone marrow stem cells mobilization on liver cells in rats with severe acute pancreatitis

Objective To observe the protective effects of autologous bone marrow mesenchymal stem cells transplantation alone with bone marrow stem cells mobilization on liver cells in rats with severe acute paucreatitis in order to explore their mechanism. Method After the establishment of severe acute pancreatitis in rats made by intraperitoneal injection of L-arginine, 240 SD rats were randomly divided into sham-operated group (n = 48), model control group (n = 48), bone marrow mesenchymal stem cell transplanted (MSC) group (n = 48), granu-lacyte-colony stimulating factor treated (G-CSF) group (n = 48) and MSC + G-CSF (n = 48). The rats of MSC group were prepared by injection of 1.2 mL MSC into femoral vein 6 hours after SAP. The rats of G-CSF group were prepared by subcutaneous injection of G-CSF 40 μg/kg for 3 days before SAP. The rats of MSC + G-CSF group received MSC and G-CSF together. The rats of sham-operated group were injected with equal volume of nor-real saline. The rats in each group were sabdivided into 12 h, 24 h, 48 h and 72 h sub-groups (n = 12) according to the examinations in different intervals after operation. Of different subgroups, the morality rate, pathological changes, expression levels of Bax, Bcl-2 proteins and apoptosis indexes of livers were observed respectively. The contents of serum TNF-α,IL-6,ALT,AST,LDH and CRP were simultaneously determined to compare the difference among subgroups by variance analysis. Results Compared to the respective model group, the mortality rates of all treated 72 h subgroups showed no difference (P > 0.05), and no rats died before 48 h. The pathological injuries of liver cells were rather attenuated in rats of treated group than in rats of control group. The liver cell apoptosis in-dexes of 48 h and 72 h MSC + G-CSF subgroups were 107.1 ± 7.0, 110.3 ± 8.6, respectively; the expression of Bax in livers of 24 h,48 h and 72 h subgroups was 5.60±0.Z5, 5.69±0.22, 5.73±0.27, respectively;Bcl-2 protein of 48 h,72 h subgroups was 4.61±0.28, 4.43±0.28, respectively; compared with MSC and G-CSF subgroups the differences were significant (P < 0.05). The serum TNF-α, IL-6, ALT, AST, LDH and CRP de-creased obviously in 24 h/48 h treated subgroups in comparison with control group (P < 0.05). The MSC + G-CSF group showed more significant effects on those biomarkers than MSC or G-CSF alone after 48 hours (P < 0.05). Conclusions Autologous bone marrow mesenchymal stem cells transplantation alonewith bone marrow stem cells mobilization can significantly protect livers from severe damage during the course of severe acute panere-atitis, and the probable mechanisms are likely associated with the pathological regeneration, anti-inflammatory ef-fect and apoptosis inhibition of MSC. Key words: Severe acute pancreatitis; Mesenchymal stem cell; Transplant; Liver; Apoptosis