Poly(Lactide-Co-Glycolide)-Monomethoxy-Poly-(Polyethylene Glycol) Nanoparticles Loaded with Melatonin Protect Adipose-Derived Stem Cells Transplanted in Infarcted Heart Tissue
Poly(Lactide-Co-Glycolide)-Monomethoxy-Poly-(Polyethylene Glycol) Nanoparticles Loaded with Melatonin Protect Adipose-Derived Stem Cells Transplanted in Infarcted Heart Tissue
复制标题
载有褪黑激素的聚（丙交酯-Co-乙交酯）-单甲氧基-聚（聚乙二醇）纳米颗粒可保护移植到梗塞心脏组织中的脂肪干细胞。
DOI：
10.1002/stem.2777
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发表时间：
2018-04-01
期刊：
影响因子：
5.2
通讯作者：
Chen, Yundai
中科院分区：
文献类型：
--
作者：
Ma, Qiang;Yang, Junjie;Chen, Yundai
干细胞移植是治疗心肌梗死的一种很有前途的策略。然而，由于缺血心脏组织中的氧化应激和炎症微环境，移植细胞面临低存活率。褪黑激素已被用作一种强大的内源性抗氧化剂，以保护细胞免受氧化损伤。然而，褪黑激素不能对不利的微环境发挥持久的作用。纳米药物递送载体具有以受控方式保护所装载的药物在生理环境中不被降解的能力，这导致更长的作用和减少的副作用。因此，我们构建了聚（丙交酯-共-乙交酯）-单甲氧基-聚（聚乙二醇）（PLGA-mPEG）纳米粒封装褪黑素。我们测试了由PLGA-mPEG纳米颗粒（褪黑激素纳米颗粒[Mel-NPs]）包封的褪黑激素对脂肪源性间充质干细胞（ADSC）的保护作用是否与游离褪黑激素相比在体外和体内增强。在体外研究中，我们发现Mel-NPs减少了p53-亲环素D复合物的形成，阻止线粒体通透性转换孔打开，并从缺氧/复氧损伤中拯救了ADSC。在大鼠心肌梗死区，Mel-NPs能获得比游离褪黑素更高的ADSC存活率，且Mel-NPs预处理的ADSC治疗效果更明显。因此，Mel-NPs和干细胞移植的组合可能是心肌梗死治疗的有希望的策略。
Stem cell transplantation is a promising therapeutic strategy for myocardial infarction. However, transplanted cells face low survival rates due to oxidative stress and the inflammatory microenvironment in ischemic heart tissue. Melatonin has been used as a powerful endogenous antioxidant to protect cells from oxidative injury. However, melatonin cannot play a long-lasting effect against the hostile microenvironment. Nano drug delivery carriers have the ability to protect the loaded drug from degradation in physiological environments in a controlled manner, which results in longer effects and decreased side effects. Therefore, we constructed poly(lactide-co-glycolide)-monomethoxy-poly-(polyethylene glycol) (PLGA-mPEG) nanoparticles to encapsulate melatonin. We tested whether the protective effect of melatonin encapsulated by PLGA-mPEG nanoparticles (melatonin nanoparticles [Mel-NPs]) on adipose-derived mesenchymal stem cells (ADSCs) was enhanced compared to that of free melatonin both in vitro and in vivo. In the in vitro study, we found that Mel-NPs reduced formation of the p53- cyclophilin D complex, prevented mitochondrial permeability transition pores from opening, and rescued ADSCs from hypoxia/reoxygenation injury. Moreover, Mel-NPs can achieve higher ADSC survival rates than free melatonin in rat myocardial infarction areas, and the therapeutic effects of ADSCs pretreated with Mel-NPs were more apparent. Hence, the combination of Mel-NPs and stem cell transplantation may be a promising strategy for myocardial infarction therapy.