Age-related changes in human hematopoietic stem/progenitor cells
Age-related changes in human hematopoietic stem/progenitor cells
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DOI：
10.1111/j.1474-9726.2011.00675.x
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发表时间：
2011-06-01
期刊：
影响因子：
7.8
通讯作者：
Goodhardt, Michele
中科院分区：
文献类型：
--
作者：
Kuranda, Klaudia;Vargaftig, Jacques;Goodhardt, Michele
成体干细胞对于维持整个生命过程中的细胞内稳态至关重要，然而年龄对其再生能力的影响却知之甚少。所有淋巴样和髓样血细胞谱系都是从人骨髓中存在的造血干细胞连续产生的。随着年龄的增长，观察到成熟血细胞的功能和组成的显着变化。在这项研究中，我们报告说，年龄相关的变化也发生在人类造血干细胞室。我们发现，多能性CD 34 + CD 38-细胞的比例在老年人（> 70岁）的骨髓中增加。CD 34 + CD 38 + CD 90-CD 45 RA +/-CD 10-和CD 34 + CD 33+髓系祖细胞在骨髓中保持相同的水平，而早期CD 34 + CD 38 + CD 90-CD 45 RA + CD 10+和定型CD 34 + CD 19 + B淋巴祖细胞的频率随年龄而降低。与衰老的小鼠模型相反，用免疫缺陷NOD/SCID/IL-2 R γ null（NSG）小鼠进行的移植实验显示，NSG再增殖细胞的频率不随年龄显著变化，并且髓系重建减少。在体外集落形成试验中也观察到CD 34+细胞生成髓系细胞能力的年龄相关性降低。因此，随着年龄的增长，人造血干/祖细胞经历数量变化以及功能修饰。
P>Adult stem cells are critical for maintaining cellular homeostasis throughout life, yet the effects of age on their regenerative capacity are poorly understood. All lymphoid and myeloid blood cell lineages are continuously generated from hematopoietic stem cells present in human bone marrow. With age, significant changes in the function and composition of mature blood cells are observed. In this study, we report that age-related changes also occur in the human hematopoietic stem cell compartment. We find that the proportion of multipotent CD34+CD38- cells increases in the bone marrow of elderly (> 70 years) individuals. CD34+CD38+CD90-CD45RA+/-CD10- and CD34+CD33+ myeloid progenitors persist at the same level in the bone marrow, while the frequency of early CD34+CD38+CD90-CD45RA+CD10+ and committed CD34+CD19+ B-lymphoid progenitors decreases with age. In contrast to mice models of aging, transplantation experiments with immunodeficient NOD/SCID/IL-2R gamma null (NSG) mice showed that the frequency of NSG repopulating cells does not change significantly with age, and there is a decrease in myeloid lineage reconstitution. An age-related decrease in the capacity of CD34+ cells to generate myeloid cells was also seen in colony-forming assays in vitro. Thus, with increasing age, human hematopoietic stem/progenitor cells undergo quantitative changes as well as functional modifications.