Leptin signaling is required for augmented therapeutic properties of mesenchymal stem cells conferred by hypoxia preconditioning.
Leptin signaling is required for augmented therapeutic properties of mesenchymal stem cells conferred by hypoxia preconditioning.
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缺氧预处理增强间充质干细胞的治疗特性需要瘦素信号传导
DOI：
10.1002/stem.1784
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发表时间：
2014-10
期刊：
影响因子：
5.2
通讯作者：
Wang, Jian'An
中科院分区：
文献类型：
--
作者：
Hu, Xinyang;Wu, Rongrong;Jiang, Zhi;Wang, Lihan;Chen, Panpan;Zhang, Ling;Yang, Lu;Wu, Yan;Chen, Han;Chen, Huiqiang;Xu, Yinchuan;Zhou, Yu;Huang, Xin;Webster, Keith A.;Yu, Hong;Wang, Jian'An
低氧预处理可增强间充质干细胞（MSCs）的治疗作用。然而，缺氧诱导的增强骨髓间充质干细胞对心肌梗死（MI）的保护作用的机制知之甚少。我们发现，缺氧增强的存活率，流动性和保护共培养的心肌细胞是通过增加瘦素和细胞表面受体CXCR 4的表达。增强的活动被取消，无论是敲低瘦素与选择性的shRNA或遗传缺陷的瘦素或其受体的MSC衍生，分别从ob/ob或db/db小鼠。为了表征瘦素在通过缺氧调节MSC功能中的作用及其对增强治疗功效的可能贡献，在急性MI的小鼠模型中实施使用源自野生型、ob/ob或db/db小鼠的MSC的细胞疗法。缺氧预处理增强的保护作用仅见于野生型小鼠的MSC。缺氧预处理对参数的影响不同，包括MSC移植，c-Kit+细胞募集到梗死，血管密度，梗死面积和长期收缩功能。这些数据表明，瘦素信号是早期和必要的步骤，增强生存，趋化性和治疗性质的间充质干细胞赋予预培养缺氧。瘦素可能在启动驻留在骨髓内膜中的MSC对系统信号分子和随后的组织修复的最佳反应中发挥生理作用。
Hypoxia preconditioning enhances the therapeutic effect of mesenchymal stem cells (MSCs). However, the mechanism underlying hypoxia-induced augmentation of the protective effect of MSCs on myocardial infarction (MI) is poorly understood. We show that hypoxia-enhanced survival, mobility, and protection of cocultured cardiomyocytes were paralleled by increased expression of leptin and cell surface receptor CXCR4. The enhanced activities were abolished by either knockdown of leptin with a selective shRNA or by genetic deficiency of leptin or its receptor in MSCs derived, respectively, from ob/ob or db/db mice. To characterize the role of leptin in the regulation of MSC functions by hypoxia and its possible contribution to enhanced therapeutic efficacy, cell therapy using MSCs derived from wild-type, ob/ob, or db/db mice was implemented in mouse models of acute MI. Augmented protection by hypoxia pretreatment was only seen with MSCs from wild-type mice. Parameters that were differentially affected by hypoxia pretreatment included MSC engraftment, c-Kit+ cell recruitment to the infarct, vascular density, infarct size, and long-term contractile function. These data show that leptin signaling is an early and essential step for the enhanced survival, chemotaxis, and therapeutic properties of MSCs conferred by preculture under hypoxia. Leptin may play a physiological role in priming MSCs resident in the bone marrow endosteum for optimal response to systemic signaling molecules and subsequent tissue repair.
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影响因子：
4.8
作者：
Gonzalez-Perez RR;Xu Y;Guo S;Watters A;Zhou W;Leibovich SJ
通讯作者：
Leibovich SJ
DOI：
10.1158/1541-7786.mcr-07-2177
发表时间：
2008-07
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Niu G;Briggs J;Deng J;Ma Y;Lee H;Kortylewski M;Kujawski M;Kay H;Cress WD;Jove R;Yu H
通讯作者：
Yu H
影响因子：
82.9
作者：
Ceradini, DJ;Kulkarni, AR;Gurtner, GC
通讯作者：
Gurtner, GC
影响因子：
3.7
作者：
Hung SC;Pochampally RR;Hsu SC;Sanchez C;Chen SC;Spees J;Prockop DJ
通讯作者：
Prockop DJ
影响因子：
168.9
作者：
Ptaszek, Leon M.;Mansour, Moussa;Chien, Kenneth R.
通讯作者：
Chien, Kenneth R.