Stokman Geurt, Leemans Jaklien C, Stroo Ingrid, Hoedemaeker Inge, Claessen Nike, Teske Gwendoline J D, Weening Jan J, Florquin Sandrine
Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Nephrol Dial Transplant. 2008 Feb;23(2):483-91. doi: 10.1093/ndt/gfm607. Epub 2007 Nov 7.
The plasticity of bone marrow-derived stem cells, also comprising haematopoietic stem cells, has been shown to extend to renal epithelial lineages. Yet, the low rate of their contribution to the injured kidney has led to questions regarding their significance in tissue repair after acute injury. We describe here the effect of stem cell mobilization therapy on the progression of renal fibrosis in a mouse model of chronic obstructive nephropathy.
Mice were subjected to unilateral ureter obstruction (UUO) and treated with stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF) or saline. Circulating cells were analysed by flow cytometry; labelled bone marrow c-KIT(HIGH) cells were injected into animals subjected to UUO. Granulocytes, macrophages, cellular proliferation or apoptosis and myofibroblasts were detected by immunostaining. Collagen deposition was determined by measuring renal hydroxyproline contents. Cytokine levels were measured by ELISA.
SCF/G-CSF treatment of mice induced significant haematopoietic stem and progenitor cell mobilization from the bone marrow. Although these cells are able to migrate to the obstructed kidney, they did not influence renal damage, fibrosis and inflammatory cell influx.
Although SCF/G-CSF treatment significantly enhanced the availability of haematopoietic stem cells to the obstructed kidney, the progression of renal fibrosis could not be delayed or halted. Our results indicate that effective stem cell mobilization does not alter renal fibrosis.
骨髓来源的干细胞，包括造血干细胞，其可塑性已被证明可扩展至肾上皮谱系。然而，它们对受损肾脏的贡献比例较低，这引发了关于其在急性损伤后组织修复中意义的疑问。我们在此描述干细胞动员疗法对慢性梗阻性肾病小鼠模型肾纤维化进展的影响。
对小鼠进行单侧输尿管梗阻（UUO），并给予干细胞因子（SCF）和粒细胞集落刺激因子（G-CSF）或生理盐水治疗。通过流式细胞术分析循环细胞；将标记的骨髓c-KIT（高表达）细胞注射到接受UUO的动物体内。通过免疫染色检测粒细胞、巨噬细胞、细胞增殖或凋亡以及肌成纤维细胞。通过测量肾脏羟脯氨酸含量来确定胶原蛋白沉积。通过酶联免疫吸附测定法测量细胞因子水平。
对小鼠进行SCF/G-CSF治疗可诱导骨髓中造血干细胞和祖细胞的显著动员。尽管这些细胞能够迁移至梗阻的肾脏，但它们并未影响肾损伤、纤维化和炎性细胞浸润。
尽管SCF/G-CSF治疗显著提高了梗阻肾脏中造血干细胞的可用性，但肾纤维化的进展并未延迟或停止。我们的结果表明，有效的干细胞动员不会改变肾纤维化。
