异基因骨髓间充质干细胞移植治疗小鼠前列腺癌的实验研究

Allogenetic Bone Marrow Derived Mesenchymal Stem Cell Transplantation for the Treatment of Prostate Cancer in Murine Model

目的观察非清髓性异基因骨髓间充质干细胞移植对小鼠前列腺移植瘤的治疗效果。方法应用全骨髓培养法培养BALB/c小鼠骨髓间充质干细胞,通过流式细胞术检测第四代细胞中CD44阳性细胞率,并通过油红染色鉴定由骨髓间充质干细胞分化的脂肪细胞。应用C57小鼠源性前列腺癌株RM-1(2×10~6/只)制成C57BL小鼠皮下移植瘤模型,分为对照组和异基因骨髓间充质干细胞移植组,每组10只。应用FC方案(氟达拉滨30mg/m^2,-d^(1-5);环磷酰胺300mg/m^2,-d^(1-3))对非对照组小鼠进行非清髓性预处理。异基因干细胞移植组小鼠经尾静脉注入骨髓间充质干细胞1×10~6个/只。记录并比较两组小鼠的肿瘤体积及生存时间。结果全骨髓培养法培养的第四代细胞中CD44阳性率为84.29%,油红染色证实由骨髓间充质干细胞自然分化的脂肪细胞存在。与对照组相比,异基因骨髓间充质干细胞移植显著的抑制了小鼠前列腺癌的生长(P=0.047),并明显延长了异基因骨髓间充质干细胞移植组小鼠的生存时间(P=0.00001)。结论异基因骨髓间充质干细胞移植显著的抑制了小鼠前列腺癌的生长,延长了受体小鼠的生存时间,预示了将骨髓间充质干细胞作为抑癌基因载体的良好前景。

Objective To explore the possible graft versus tumor(GVT)effects induced by allogenetic bone marrow derived mesenchymal stem cell(MSC)transplantation in murine prostate cancer model.Methods Bone marrow cells were cultured and purified by adherent method to the fourth generation.The MSCs were then identified by flow cytometry for CD44 positive cells and oil red stain for the differentiated fat cells.Following nonmye-loablative regimens consisted of fludarabine(30mg/m^2,-d^(1-5))and cyclophosphamide(300mg/m^2,-d^(1-3)), C57BL mice bearing RM-1(2×10~6 each)tumors underwent an allogeneic bone marrow MSCs(2×10~6 each) transplantation and bone marrow cells(5×10~6 each)and spleen cells(1×10~7 each)transplantation from BALB/ c donors through the tail veins.The tumor volumes and survival time were recorded,and then compared with the control group.Results The percentage of CD44 positive cells in the fourth generation was 84.29%,and the oil red stain proved the existence of differentiated fat cells.Comparing with the control group,allogenetic bone marrow derived MSC transplantation inhibited the growth of the tumors and prolonged the recipients' survival time significantly(P=0.047 and 0.00001,respectively).Conclusions Allogenetic bone marrow derived MSC transplantation inhibited the growth of the tumors and prolonged the recipients' survival time significantly,which suggesting its promising future as a functional tumor-specific delivery vehicle.