Impact of modeled microgravity on migration, differentiation, and cell cycle control of primitive human hematopoietic progenitor cells
Impact of modeled microgravity on migration, differentiation, and cell cycle control of primitive human hematopoietic progenitor cells
复制标题
DOI：
10.1016/j.exphem.2004.03.014
复制
发表时间：
2004-08-01
影响因子：
2.6
通讯作者：
Orschell, CM
中科院分区：
文献类型：
--
作者：
Plett, PA;Abonour, R;Orschell, CM
Objective.骨髓造血干细胞的迁移、增殖和分化。是维持造血稳态的重要因素。在暴露于微重力（R-g）的人体中，红细胞和淋巴细胞的稳态控制受到干扰，导致空间飞行引起的贫血和免疫抑制。我们试图确定这些异常是否可以用μ g诱导的人类BM CD 34（+）细胞迁移、增殖和分化的变化来解释，以及这些变化是否可以开始解释在宇航员中观察到的造血稳态的任何变化。使用NASA的旋转壁容器（RWV）以模拟μ g（mmu-g）培养BM CD 34（+）细胞，或在地球重力下以对照培养物培养BM CD 34（+）细胞2至18天。在不同的时间收获细胞，评估CD 34（+）细胞的迁移能力、细胞周期动力学和调节蛋白以及成熟状态。骨髓CD 34（+）细胞在RWV中培养2 - 3天，导致基质细胞衍生因子1（SDF-1 α）定向迁移显著减少，这与F-肌动蛋白表达减少相关。模拟μ-g诱导细胞周期动力学的改变，其特征在于S期延长和细胞周期蛋白A表达减少。原始CD 34（+）细胞在RWV中培养14 ~ 18 d后，其分化有利于髓系细胞的发育，但红系细胞的发育受到抑制，与对照组相比，红系细胞的发育明显减少。这些结果表明，mmu-g显着抑制原始BM CD 34（+）细胞的迁移潜力，细胞周期进程和分化模式，这可能有助于在太空飞行期间观察到的人类血液学异常。(C)2004年国际实验血液学学会。爱思唯尔公司出版
Objective. Migration, proliferation, and differentiation of bone marrow (BM) hematopoietic stem cells (HSC). are important factors in maintaining hematopoietic homeostasis. Homeostatic control of erythrocytes and lymphocytes is perturbed in humans exposed to microgravity (R-g), resulting in space flight-induced anemia and immunosuppression. We sought to determine whether any of these anomalies can be explained by mu-g-induced changes in migration, proliferation, and differentiation of human BM CD34(+) cells, and whether such changes can begin to explain any of the shifts in hematopoietic homeostasis observed in astronauts.Materials and Methods. BM CD34(+) cells were cultured in modeled mu-g (mmu-g) using NASA's rotating wall vessels (RWV), or in control cultures at earth gravity for 2 to 18 days. Cells were harvested at different times and CD34(+) cells assessed for migration potential, cell-cycle kinetics and regulatory proteins, and maturation status.Results. Culture of BM CD34(+) cells in RWV for 2 to 3 days resulted in a significant reduction of stromal cell-derived factor 1 (SDF-1alpha)-directed migration, which correlated with decreased expression of F-actin. Modeled mu-g induced alterations in cell-cycle kinetics that were characterized by prolonged S phase and reduced cyclin A expression. Differentiation of primitive CD34(+) cells cultured for 14 to 18 days in RWV favored myeloid cell development at the expense of erythroid development, which was significantly reduced compared to controls.Conclusions. These results illustrate that mmu-g significantly inhibits the migration potential, cell-cycle progression, and differentiation patterns of primitive BM CD34(+) cells, which may contribute to some of the hematologic abnormalities observed in humans during space flight. (C) 2004 International Society for Experimental Hematology. Published by Elsevier Inc.