Hypoxic Preconditioning Enhances Angiogenic Potential of Bone Marrow Cells With Aging-Related Functional Impairment

Hypoxic Preconditioning Enhances Angiogenic Potential of Bone Marrow Cells With Aging-Related Functional Impairment
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DOI:
10.1253/circj.cj-11-0605
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发表时间:
2012-04-01
影响因子:
3.3
通讯作者:
Haman, Kimikazu
Haman, Kimikazu
中科院分区:
医学3区
文献类型:
--
作者:
Kubo, Masayuki;Li, Tao-Sheng;Haman, Kimikazu

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背景:对年轻健康个体的骨髓细胞(BMC)进行低氧预处理可以增强细胞的治疗潜力。考虑到细胞质量不同,对缺氧的反应可能有所不同,我们评估了低氧预处理对老年小鼠BMC的影响,并比较了老年和年轻小鼠BMC之间的反应差异。 方法和结果:将年轻(3个月)和老年(20-22个月)小鼠的BMC在2% O-2中培养24小时进行低氧预处理。与年轻小鼠的BMC相比,老年小鼠的BMC表现出明显更少的CD34或c-kit阳性干细胞、更高的p53表达和更低的端粒酶活性。老年小鼠的 BMC 的粘附力、存活率和血管生成效力也较低,表明存在与衰老相关的损伤。通过体外评估以及体内植入缺血后肢,来自老年小鼠的缺氧预处理的 BMC 显示出增强的粘附力、存活率和血管生成能力。低氧预处理的所有增强作用在老年和年轻小鼠的 BMC 之间具有可比性,尽管与年轻小鼠相比,有或没有低氧预处理的 BMC 的血管生成潜力在老年小鼠中较低。结论:老年和年轻小鼠的 BMC 对缺氧的相似反应表明,低氧预处理可能是增强 BMC 血管生成潜力的有效方法。 (Circ J 2012;76:986-994)
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 24h in 2% O-2. 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. (Circ J 2012; 76: 986-994)