Inhibition of NF-κB improves the stress resistance and myogenic differentiation of MDSPCs isolated from naturally aged mice.
Inhibition of NF-κB improves the stress resistance and myogenic differentiation of MDSPCs isolated from naturally aged mice.
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DOI：
10.1371/journal.pone.0179270
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Huard J
中科院分区：
文献类型：
--
作者：
Proto JD;Lu A;Dorronsoro A;Scibetta A;Robbins PD;Niedernhofer LJ;Huard J
成体干细胞的再生能力随着衰老而下降，这是有据可查的。由于这种下降，自体干细胞疗法的疗效可能会随着捐赠者年龄的增加而下降。在这些情况下，恢复衰老干细胞功能的策略将具有临床实用性。在全球范围内，转录因子 NF-κB 在衰老组织中表达上调。鉴于 NF-κB 在肌生成中发挥的负面作用，我们研究了是否可以通过抑制 NF-κB 来改善与年龄相关的肌肉源性干细胞/祖细胞 (MDSPC) 功能下降。在此，我们证明对 NF-κB 激活的药理学或遗传抑制可增加肌原性分化并提高对氧化应激的抵抗力。我们的结果表明，MDSPC“衰老”可能是可逆的，并且针对 NF-κB 等途径的药理学靶向可能会增强细胞疗法的功效。
A decline in the regenerative capacity of adult stem cells with aging is well documented. As a result of this decline, the efficacy of autologous stem cell therapies is likely to decline with increasing donor age. In these cases, strategies to restore the function of aged stem cells would have clinical utility. Globally, the transcription factor NF-κB is up-regulated in aged tissues. Given the negative role that NF-κB plays in myogenesis, we investigated whether the age-related decline in the function of muscle-derived stem/progenitor cells (MDSPCs) could be improved by inhibition of NF-κB. Herein, we demonstrate that pharmacologic or genetic inhibition of NF-κB activation increases myogenic differentiation and improves resistance to oxidative stress. Our results suggest that MDSPC “aging” may be reversible, and that pharmacologic targeting of pathways such as NF-κB may enhance the efficacy of cell-based therapies.