Endothelial progenitor cell proliferation and differentiation is regulated by erythropoietin - Rapid communication
Endothelial progenitor cell proliferation and differentiation is regulated by erythropoietin - Rapid communication
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DOI：
10.1046/j.1523-1755.2003.00279.x
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发表时间：
2003-11-01
影响因子：
19.6
通讯作者：
Fliser, D
中科院分区：
文献类型：
--
作者：
Bahlmann, FH;DeGroot, K;Fliser, D
背景。循环骨髓源性内皮祖细胞 (EPC) 促进血管修复过程。在人类中，它们的数量与内皮功能和心血管风险相关。我们测试了达贝泊汀阿尔法 [即细胞因子促红细胞生成素 (EPO) 的重组类似物] 刺激 EPC 增殖和分化的假设。方法。我们使用流式细胞术评估了全血中的 CD34+ 循环干细胞 (cSC)，此外，在 8 名肾性贫血患者接受标准达贝泊汀治疗 6 周期间，我们还通过体外测定评估了 EPC 的增殖/分化。结果。达贝泊汀治疗导致 CD34+ cSC 数量显着增加（第 2 周，193%+/- 46%；第 6 周，298%+/- 90%；与基线相比，P < 0.05）。此外，达贝泊汀显着增加了功能活跃的 EPC 数量（第 2 周，256%+/- 48%；第 6 周，299%+/- 59%；与基线相比，两者 P < 0.01）。达贝泊汀对管形成试验中评估的 EPC 功能活性的影响是剂量依赖性的。给予达贝泊汀引起培养的 EPC 中蛋白激酶 B (Akt) 的激活。结论。达贝泊汀标准治疗可显着增强肾脏患者的 EPC 增殖和分化。使用重组 EPO 类似物可能是治疗血管病变患者的一种新颖且安全的治疗方法。
Background. Circulating bone marrow-derived endothelial progenitor cells (EPCs) promote vascular reparative processes. In humans, their number correlate with endothelial function and cardiovascular risk. We tested the hypothesis that darbepoetin alfa [i.e., a recombinant analogue of the cytokine erythropoietin (EPO)] stimulates proliferation and differentiation of EPCs.Methods. We assessed CD34+ circulating stem cells (cSCs) in whole blood using flow cytometry and, in addition, proliferation/differentiation of EPCs in an in-vitro assay during 6 weeks of a standard darbepoetin therapy in eight patients with renal anemia.Results. Darbepoetin treatment caused a significant increase in the number of CD34+ cSCs (week 2, 193%+/- 46%; and week 6, 298%+/- 90%; P < 0.05 vs. baseline). In addition, darbepoetin markedly increased the number of functionally active EPCs (week 2, 256%+/- 48%; and week 6, 299%+/- 59%; both P < 0.01 vs. baseline). The effect of darbepoetin on functional activity of EPCs assessed in a tube formation assay was dose dependent. Administration of darbepoietin caused activation of protein kinase B (Akt) in cultured EPCs.Conclusion. A standard treatment with darbepoetin markedly enhances EPC proliferation and differentiation in renal patients. The use of recombinant EPO analogues may be a novel and safe therapeutic approach in patients with vascular pathology.