Mesenchymal stem cells deliver exogenous miR-21 via exosomes to inhibit nucleus pulposus cell apoptosis and reduce intervertebral disc degeneration.
Mesenchymal stem cells deliver exogenous miR-21 via exosomes to inhibit nucleus pulposus cell apoptosis and reduce intervertebral disc degeneration.
复制标题
间充质干细胞通过外泌体传递外源性miR-21抑制髓核细胞凋亡并减少椎间盘退变
DOI：
10.1111/jcmm.13316
复制
发表时间：
2018-01
影响因子：
5.3
通讯作者：
Zhao J
中科院分区：
文献类型：
--
作者：
Cheng X;Zhang G;Zhang L;Hu Y;Zhang K;Sun X;Zhao C;Li H;Li YM;Zhao J
虽然间充质干细胞（mesenchymal stem cells，MSCs）移植到椎间盘（IVD）内可能有助于抑制髓核细胞（nucleus pulposus cells，NPC）凋亡，减轻IVD退变，但其治疗机制尚未完全阐明。本研究的目的是探讨MSC-exosomes对鼻咽癌细胞凋亡和IVD变性的保护作用，并研究MSC-exosomes中miRNA对鼻咽癌细胞凋亡的调控作用及其相关机制。从MSC培养基中分离MSC-外泌体，并在细胞和大鼠模型中评估其抗凋亡作用。鉴定凋亡NPC中下调的miRNA，并检测其在MSC-外泌体中的含量。对筛选出的miRNAs的靶基因及可能的下游通路进行了研究。纯化的MSC-外泌体被NPC摄取并抑制NPC凋亡。miR-21的水平在凋亡的NPC中下调，而MSC-外来体富含miR-21。外泌体miR-21可通过磷脂酰肌醇3-激酶（PI 3 K）-Akt通路靶向磷酸酶和张力蛋白同源物（PTEN），转移到NPC中，减轻TNF-α诱导的NPC凋亡。椎间盘内注射MSC‐exosomes减轻了大鼠模型中NPC细胞凋亡和IVD变性。总之，MSC衍生的外泌体至少部分地通过外泌体中含有的miR-21防止NPC凋亡过程并减轻IVD变性。外泌体miR-21抑制PTEN，从而激活凋亡NPC中的PI 3 K/Akt通路。我们的工作为IVD变性提供了一种有前途的治疗策略。
Although mesenchymal stem cells (MSCs) transplantation into the IVD (intervertebral disc) may be beneficial in inhibiting apoptosis of nucleus pulposus cells (NPCs) and alleviating IVD degeneration, the underlying mechanism of this therapeutic process has not been fully explained. The purpose of this study was to explore the protective effect of MSC‐derived exosomes (MSC‐exosomes) on NPC apoptosis and IVD degeneration and investigate the regulatory effect of miRNAs in MSC‐exosomes and associated mechanisms for NPC apoptosis. MSC‐exosomes were isolated from MSC medium, and its anti‐apoptotic effect was assessed in a cell and rat model. The down‐regulated miRNAs in apoptotic NPCs were identified, and their contents in MSC‐exosomes were detected. The target genes of eligible miRNAs and possible downstream pathway were investigated. Purified MSC‐exosomes were taken up by NPCs and suppressed NPC apoptosis. The levels of miR‐21 were down‐regulated in apoptotic NPCs while MSC‐exosomes were enriched in miR‐21. The exosomal miR‐21 could be transferred into NPCs and alleviated TNF‐α induced NPC apoptosis by targeting phosphatase and tensin homolog (PTEN) through phosphatidylinositol 3‐kinase (PI3K)‐Akt pathway. Intradiscal injection of MSC‐exosomes alleviated the NPC apoptosis and IVD degeneration in the rat model. In conclusion, MSC‐derived exosomes prevent NPCs from apoptotic process and alleviate IVD degeneration, at least partly, via miR‐21 contained in exosomes. Exosomal miR‐21 restrains PTEN and thus activates PI3K/Akt pathway in apoptotic NPCs. Our work confers a promising therapeutic strategy for IVD degeneration.
登录
查看更多内容
影响因子：
4.8
作者：
Akyurekli, Celine;Le, Yevgeniya;Allan, David S.
通讯作者：
Allan, David S.
影响因子：
3.7
作者：
Liu G;Cao P;Chen H;Yuan W;Wang J;Tang X
通讯作者：
Tang X
影响因子：
--
作者：
Ma, Jin Feng;Zang, Li Na;Zou, Debo
通讯作者：
Zou, Debo
影响因子：
3.3
作者：
Kumar, Deepak;Lyness, Alex;Liu, Yang
通讯作者：
Liu, Yang
影响因子：
168.9
作者：
通讯作者：
--