Shima Haruko, Takubo Keiyo, Iwasaki Hiroko, Yoshihara Hiroki, Gomei Yumiko, Hosokawa Kentaro, Arai Fumio, Takahashi Takao, Suda Toshio
Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Biochem Biophys Res Commun. 2009 Jan 16;378(3):467-72. doi: 10.1016/j.bbrc.2008.11.056. Epub 2008 Nov 24.
Hematopoietic stem cells (HSCs) reside in hypoxic areas of the bone marrow. However, the role of hypoxia in the maintenance of HSCs has not been fully characterized. We performed xenotransplantation of human cord blood cells cultured in hypoxic or normoxic conditions into adult NOD/SCID/IL-2Rgamma(null) (NOG) mice. Hypoxic culture (1% O(2)) for 6 days efficiently supported the maintenance of HSCs, although cell proliferation was suppressed compared to the normoxic culture. In contrast, hypoxia did not affect in vitro colony-forming ability. Upregulation of a cell cycle inhibitor, p21, was observed in hypoxic culture. Immunohistochemical analysis of recipient bone marrow revealed that engrafted CD34(+)CD38(-) cord blood HSCs were hypoxic. Taken together, these results demonstrate the significance of hypoxia in the maintenance of quiescent human cord blood HSCs.
造血干细胞(HSCs)存在于骨髓的低氧区域。然而,低氧在造血干细胞维持中的作用尚未完全明确。我们将在低氧或常氧条件下培养的人脐带血细胞异种移植到成年NOD/SCID/IL-2Rγ(null)(NOG)小鼠体内。低氧培养(1% O₂)6天能有效维持造血干细胞,尽管与常氧培养相比细胞增殖受到抑制。相反,低氧并不影响体外集落形成能力。在低氧培养中观察到细胞周期抑制剂p21上调。对受体骨髓的免疫组织化学分析显示,移植的CD34⁺CD38⁻脐带血造血干细胞处于低氧状态。综上所述,这些结果证明了低氧在维持静止的人脐带血造血干细胞中的重要性。