骨髓间充质细胞和单个核细胞移植对糖尿病小鼠胰岛功能的影响

目的 比较骨髓间充质细胞移植和单个核细胞移植对糖尿病小鼠胰岛功能影响的差异.方法 建立糖尿病小鼠模型并分成3组:对照组(n=14)通过尾静脉注射磷酸盐缓冲液(PBS);单个核细胞组(n=14)通过尾静脉移植骨髓单个核细胞;间充质细胞组(n=14)通过尾静脉移植骨髓间充质细胞.观察移植后1周(n=6)和移植后6周(n=8),各组小鼠血糖的变化、胰岛数量、胰腺组织形态学特征及相关标记物的表达.结果 移植后1周,间充质细胞组小鼠血糖出现显著下降(16.6±1.6)mmol/L,与对照组(26.3±0.5)mmol/L和单个核细胞移植组(24.4±1.3)mmol/L比较差异有统计学意义(P＜0.05),并一直维持到移植后第6周,血糖下降到(16.5±1.5)mmol/L,与对照组(27.7±0.1)mmol/L比较差异有统计学意义(P＜0.05);移植后1周,间充质细胞组小鼠胰岛数目(21.2±1. 1)和胰岛β细胞数目(415.9±25.4)显著增加,与对照组(11.2±1.3)/(65.9±7.1)和单个核细胞组(12.2±1.3)/(64.1±6.5)比较差异均有统计学意义(P均＜0.05).单个核细胞组和间充质细胞组小鼠胰岛中均发现BrdU(+)Insulin(+)细胞和BrdU(+)Insulin(-)细胞.结论 骨髓间充质细胞移植改善糖尿病小鼠胰岛功能的效果优于骨髓单个核细胞移植.移植后胰岛的再生既来源于胰岛β细胞的增殖,也可能来源于胰岛干细胞的分化.

Abstract：

Objective To compare the different effects of bone marrow mononuclear cells vs mesenchymal cells transplantation on islets function of diabetic mice. Methods Mouse diabetic models were created by multiply peritoneal injection of low-dose streptozotocin (STZ) and divided into three groups:control group ( n = 14) , bone marrow mononuclear cells group ( n = 14) , and bone marrow mesenchymal cells group (n = 14). Blood glucose was measured weekly after transplantation by glucometer. Histochem istry and immunofluorescence were performed to characterize pancreatic histology, morphology and markers expressed in receipt pancreas. Results Compared with control group and bone marrow mesenchymal cells group, blood glucose levels in bone marrow mesenchymal cells group were significantly reduced at first week after transplantation[( 16. 6 ± 1.6 ) vs ( 26. 3 ± 0. 5 ) / ( 24. 4 ± 1.3 ) mmol/L, P ＜ 0. 05]and sustained to reduce at 6th week after transplantation[( 16. 5 ± 1.5 ) vs ( 27.7 ± 0. 1 ) mmol/L in control group,P＜0. 05]. One week after transplantation, the islets number in bone marrow mesenchymal cells group was larger than in control group ( 21.2 ± 1. 1vs 11.2 ± 1.3, P ＜ 0. 05 ) and bone marrow mononuclear cells group ( 21.2 ± 1. 1vs 12. 2 ± 1.3 ,P ＜0. 05 ). One weeks after transplantation, the beta cell number in bone marrow mesenchymal cells group was larger than in control group (415.9 ± 25.4 vs 65.9 ±7. 1,P＜0.05) and bone marrow mononuclear cells group (415.9 ±25.4 vs 64. 1 ±6.5,P＜0.05). In bone marrow mononuclear cells and bone marrow mesenchymal cells groups, there were several BrdU ( + )Insulin( - ) cells and BrdU( + )Insulin( - ) cells in the islets. Conclusion The effect of bone marrow mesenchymal cells transplantation to improve diabetic islet function is more satisfactory than bone marrow mononuclear cells transplantation. Bone marrow mesenchymal cells transplantation can initiate pancreatic islets β cells regeneration by both proliferation of β cells and differentiation of pancreatic stem cells.

Comparative study on bone marrow mononuclear cells vs mesenchymal cells transplantation to improve islets function of diabetic mice

Objective To compare the different effects of bone marrow mononuclear cells vs mesenchymal cells transplantation on islets function of diabetic mice. Methods Mouse diabetic models were created by multiply peritoneal injection of low-dose streptozotocin (STZ) and divided into three groups:control group ( n = 14) , bone marrow mononuclear cells group ( n = 14) , and bone marrow mesenchymal cells group (n = 14). Blood glucose was measured weekly after transplantation by glucometer. Histochem istry and immunofluorescence were performed to characterize pancreatic histology, morphology and markers expressed in receipt pancreas. Results Compared with control group and bone marrow mesenchymal cells group, blood glucose levels in bone marrow mesenchymal cells group were significantly reduced at first week after transplantation[( 16. 6 ± 1.6 ) vs ( 26. 3 ± 0. 5 ) / ( 24. 4 ± 1.3 ) mmol/L, P ＜ 0. 05]and sustained to reduce at 6th week after transplantation[( 16. 5 ± 1.5 ) vs ( 27.7 ± 0. 1 ) mmol/L in control group,P＜0. 05]. One week after transplantation, the islets number in bone marrow mesenchymal cells group was larger than in control group ( 21.2 ± 1. 1vs 11.2 ± 1.3, P ＜ 0. 05 ) and bone marrow mononuclear cells group ( 21.2 ± 1. 1vs 12. 2 ± 1.3 ,P ＜0. 05 ). One weeks after transplantation, the beta cell number in bone marrow mesenchymal cells group was larger than in control group (415.9 ± 25.4 vs 65.9 ±7. 1,P＜0.05) and bone marrow mononuclear cells group (415.9 ±25.4 vs 64. 1 ±6.5,P＜0.05). In bone marrow mononuclear cells and bone marrow mesenchymal cells groups, there were several BrdU ( + )Insulin( - ) cells and BrdU( + )Insulin( - ) cells in the islets. Conclusion The effect of bone marrow mesenchymal cells transplantation to improve diabetic islet function is more satisfactory than bone marrow mononuclear cells transplantation. Bone marrow mesenchymal cells transplantation can initiate pancreatic islets β cells regeneration by both proliferation of β cells and differentiation of pancreatic stem cells.