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低氧预处理增强了与年龄相关功能障碍的骨髓细胞的血管生成潜能。

Hypoxic preconditioning enhances angiogenic potential of bone marrow cells with aging-related functional impairment.

机构信息

Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.

出版信息

Circ J. 2012;76(4):986-94. doi: 10.1253/circj.cj-11-0605. Epub 2012 Feb 1.

DOI:10.1253/circj.cj-11-0605
PMID:22293445
Abstract

BACKGROUND

Hypoxic preconditioning of bone marrow cells (BMCs) from young healthy individuals can enhance the cells' therapeutic potential. Considering that the response to hypoxia may differ according to the quality of the cells, we assessed the effect of hypoxic preconditioning on BMCs from aged mice and compared the difference in response between BMCs from aged and young mice.

METHODS AND RESULTS

BMCs from young (3 months) and aged (20-22 months) mice were subjected to hypoxic preconditioning by culture for 24 h in 2% O₂. Compared with BMCs from young mice, those from aged mice showed significantly fewer CD34- or c-kit-positive stem cells, higher expression of p53, and lower telomerase activity. Adhesion, survival and angiogenic potency were also lower in BMCs from aged mice, indicating an aging-related impairment. Hypoxia-preconditioned BMCs from aged mice showed enhanced adhesion, survival, and angiogenic potency with the in vitro assessments, as well as the in vivo implantation into ischemic hindlimbs. All the enhancements by hypoxic preconditioning were comparable between BMCs from aged and young mice, although the angiogenic potential of BMCs with and without hypoxic preconditioning was lower in old mice compared with young mice.

CONCLUSIONS

Similar responses to hypoxia by BMCs from both aged and young mice suggest that hypoxic preconditioning could be a useful method of enhancing the angiogenic potential of BMCs.

摘要

背景

对来自年轻健康个体的骨髓细胞(BMCs)进行低氧预处理可以增强细胞的治疗潜力。考虑到细胞对低氧的反应可能因细胞质量而异,我们评估了低氧预处理对老年小鼠 BMCs 的影响,并比较了老年和年轻小鼠 BMCs 反应的差异。

方法和结果

将来自年轻(3 个月)和老年(20-22 个月)小鼠的 BMCs 在 2% O₂中培养 24 h 进行低氧预处理。与年轻小鼠的 BMCs 相比,老年小鼠的 BMCs 中 CD34-或 c-kit 阳性干细胞明显较少,p53 表达较高,端粒酶活性较低。老年小鼠的 BMCs 黏附、存活和血管生成能力也较低,表明存在与衰老相关的损伤。体外评估和体内植入缺血性后肢后,低氧预处理后的老年小鼠 BMCs 的黏附、存活和血管生成能力增强。尽管与年轻小鼠相比,低氧预处理前后 BMCs 的血管生成潜力在老年小鼠中较低,但低氧预处理对老年和年轻小鼠 BMCs 的所有增强作用相当。

结论

来自老年和年轻小鼠的 BMCs 对低氧的相似反应表明,低氧预处理可能是增强 BMCs 血管生成潜力的一种有用方法。

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