Parathyroid hormone effectively induces mobilization of progenitor cells without depletion of bone marrow
Parathyroid hormone effectively induces mobilization of progenitor cells without depletion of bone marrow
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DOI：
10.1016/j.exphem.2008.03.014
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发表时间：
2008-09-01
影响因子：
2.6
通讯作者：
Franz, Wolfgang-Michael
中科院分区：
文献类型：
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作者：
Brunner, Stefan;Zaruba, Marc-Michael;Franz, Wolfgang-Michael
Objective.细胞因子介导的造血干细胞动员已成为自体和异基因干细胞移植领域的既定方法。此外，它提出了组织修复和再生医学的新概念。在本研究中，我们探讨了效力的甲状旁腺激素（PTH）相比，粒细胞集落刺激因子（G-CSF）动员的干细胞和其再生能力的骨髓。用PTH、G-CSF或盐水处理健康小鼠。使用血液细胞分析仪分析实验室参数。流式细胞仪检测造血干细胞lin（-）/Sca-1（+）/c-kit（+），CD 45（+）/CD 34（+）和CD 45（+）/CD 34（-）细胞亚群CD 31（+）、c-kit（+）、Sca-1（+）、CXCR 4（+）。免疫组织学以及荧光激活细胞分选分析被用来确定骨髓细胞的组成和细胞周期状态。酶联免疫吸附试验测定血清中不同细胞因子（G-CSF，血管内皮生长因子[VEGF]）的水平。此外，在PTH与G-CSF或G-CSF抗体组合治疗后测量循环细胞。与G-CSF相似，PTH刺激显示外周血中骨髓源性祖细胞（BMC）的所有特征性亚群显著增加（1.5至9.8倍）。与G-CSF相比，PTH处理导致骨髓中lin（-）/Sca-1（+）/c-kit（+）细胞和CD 45 +/CD 34+亚群水平恒定的细胞增殖增强。有趣的是，甲状旁腺激素的应用与血清G-CSF水平升高（2.8倍）相关，而血管内皮生长因子没有显示出显着变化。用抗体阻断内源性G-CSF显著减少了PTH治疗后循环细胞的数量。联合应用PTH和G-CSF比单独应用PTH或G-CSF有轻微的额外作用。PTH有效诱导祖细胞的动员，这可能与G-CSE的内源性释放有关。与G-CSF治疗相反，PTH不会导致骨髓耗竭，这可能是由成骨细胞上PTH受体的激活介导的。PTH对骨髓基质细胞动员和再生的新功能可能为骨髓和干细胞移植以及缺血性疾病领域的新治疗选择铺平道路。(C)2008 ISEH -血液学和干细胞学会。爱思唯尔公司出版。
Objective. Cytokine-mediated mobilization of hematopoietic stem cells has become an established method in the field of autologous and allogenic stem cell transplantation. Furthermore, it presents a new concept in tissue repair and regenerative medicine. In the present study, we explored the potency of parathyroid hormone (PTH) compared to granulocyte colony-stimulating factor (G-CSF) for mobilization of stem cells and its regenerative capacity on bone marrow.Materials and Methods. Healthy mice were either treated with PTH, G-CSF, or saline. Laboratory parameters were analyzed using a hematological cell analyzer. Hematopoietic stem cells characterized by lin(-)/Sca-1(+)/c-kit(+), as well as subpopulations (CD31(+), c-kit(+), Sca-1(+), CXCR4(+)) of CD45(+)/CD34(+) and CD45(+)/CD34(-) cells were measured by flow cytometry. Immunohistology as well as fluorescein-activated cell sorting analyses were utilized to determine the composition and cell-cycle status of bone marrow cells. Serum levels of distinct cytokines (G-CSF, vascular endothelial growth factor [VEGF]) were determined by enzyme-linked immunosorbent assay. Further, circulating cells were measured after PTH treatment in combination with G-CSF or a G-CSF antibody.Results. Stimulation with PTH showed a significant increase of all characterized subpopulations of bone marrow-derived progenitor cells (BMCs) in peripheral blood (1.5- to 9.8-fold) similar to G-CSF. In contrast to G-CSF, PTH treatment resulted in an enhanced cell proliferation with a constant level of lin(-)/Sca-1(+)/c-kit(+) cells and CD45+/CD34+ subpopulations in bone marrow. Interestingly, PTH application was associated with increased serum levels of G-CSF (2.8-fold), whereas VEGF showed no significant changes. Blocking endogenous G-CSF with an antibody significantly reduced the number of circulating cells after PTH treatment. A combination of PTH and G-CSF showed slight additional effects compared to PTH or G-CSF alone.Conclusion. PTH induces mobilization of progenitor cells effectively, which can be related to an endogenous release of G-CSE In contrast to G-CSF treatment, PTH does not result in a depletion of bone marrow, which may be mediated by an activation of PTH receptor on osteoblasts. The novel function of PTH on mobilization and regeneration of BMCs may pave the way for new therapeutic options in bone marrow and stem cell transplantation as well as in the field of ischemic disorders. (C) 2008 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.