Increased Expression of CXCR4 and Integrin αM in Hypoxia-Preconditioned Cells Contributes to Improved Cell Retention and Angiogenic Potency
Increased Expression of CXCR4 and Integrin αM in Hypoxia-Preconditioned Cells Contributes to Improved Cell Retention and Angiogenic Potency
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DOI：
10.1002/jcp.21803
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发表时间：
2009-08-01
影响因子：
5.6
通讯作者：
Hamano, Kimikazu
中科院分区：
文献类型：
--
作者：
Kubo, Masayuki;Li, Tao-Sheng;Hamano, Kimikazu
基于细胞的血管生成是治疗缺血性疾病的一种有前途的方法，但植入细胞在目标组织中的保留较差是一个主要缺点。我们测试了低氧预处理是否增加了缺血组织中植入细胞的保留和血管生成效力。小鼠外周血单核细胞 (PBNC) 在 2% O-2 下培养 24 小时进行缺氧预处理。使用常氧培养的 PBMNC 作为对照。低氧预处理增加了 PBMNC 的粘附能力。此外，缺氧修复的 PBMNC 中整合素 α M 和 CXCR4 的表达显着高于常氧培养的 PBMNC。有趣的是，缺血后肢中细胞间粘附分子-1（ICAM-1）（整合素αM的配体）和基质细胞衍生因子-1（SDF-1）（CXCR4的趋化因子）的表达显着增加。肌内植入缺血后肢3天后，缺氧预处理的PBMNCs的保留率显着高于常氧培养的PBMNCs。我们还注意到，治疗 14 天后，植入缺氧预处理的 PBMNC 的缺血后肢的血流量比植入常氧培养的 PBMNC 的缺血后肢的血流量更好。此外，整合素αM和CXCR4的抗体中和完全消除了缺氧预处理的PBMNC在植入缺血后肢后增加的细胞保留和血管生成能力。这些结果表明，植入细胞的低氧预处理是通过增加其保留来增强治疗性血管生成的可行方法。 J.细胞。生理学。 220: 508-514, 2009。(C) 2009 Wiley-Liss, Inc.
Cell-based angiogenesis is a promising method for the treatment of ischemic diseases, but the poor retention of implanted cells in targeted tissues is a major drawback. We tested whether hypoxic preconditioning increased retention and angiogenic potency of implanted cells in ischemic tissue. Hypoxic preconditioning of mouse peripheral blood mononuclear cells (PBMNCs) was done with 24 h of culture under 2% O-2. Normoxia-cultured PBMNCs were used as a control. Hypoxic preconditioning increased the adhesion capacity of the PBMNCs. Moreover, the expression of integrin alpha M and CXCR4 was significantly higher in the hypoxia-p reconditioned PBMNCs than in the normoxia-cultured PBMNCs. Interestingly, the expression of intercellular adhesion molecule-1 (ICAM-1), a ligand of integrin alpha M, and stromal cell-derived factor-1 (SDF-1), a chemokine for CXCR4, were remarkably increased in the ischemic hindlimbs. The retention of the hypoxia-preconditioned PBMNCs was significantly higher than that of the normoxia-cultured PBMNCs, 3 days after their intramuscular implantation into ischemic hindlimbs. We also noted better blood flow in the ischemic hindlimbs implanted with the hypoxia-preconditioned PBMNCs than in those implanted with the normoxia-cultured PBMNCs, 14 days after treatment. Furthermore, antibody neutralization of integrin alpha M and CXCR4 abolished completely the increased cell retention and angiogenic potency of the hypoxia-preconditioned PBMNCs after implantation into the ischemic hindlimbs. These results indicate that hypoxic preconditioning of implanted cells is a feasible method of enhancing therapeutic angiogenesis by increasing their retention. J. Cell. Physiol. 220: 508-514, 2009. (C) 2009 Wiley-Liss, Inc.