Magnetization of mesenchymal stem cells using magnetic liposomes enhances their retention and immunomodulatory efficacy in mouse inflamed skeletal muscle
Magnetization of mesenchymal stem cells using magnetic liposomes enhances their retention and immunomodulatory efficacy in mouse inflamed skeletal muscle
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DOI：
10.1016/j.ijpharm.2021.120298
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发表时间：
2021-01-30
影响因子：
5.8
通讯作者：
Fujita, Takuya
中科院分区：
文献类型：
--
作者：
Kono, Yusuke;Takegaki, Junya;Fujita, Takuya
肌肉减少症是一种与年龄相关的骨骼肌质量和力量下降的疾病，主要由慢性炎症引起。由于间充质干细胞（MSCs）具有促进肌细胞分化和抑制炎症的能力，它们是治疗肌肉减少症的有希望的候选者。在这项研究中，为了实现间充质干细胞在骨骼肌中的长期留存，我们使用先前开发的磁性阴离子脂质体/去端肽胶原复合物制备了磁化的间充质干细胞，并评估了它们在小鼠发炎骨骼肌中的留存效率和免疫调节作用。在磁场作用下，将小鼠间充质干细胞与磁性阴离子脂质体/去端肽胶原复合物孵育30分钟，可有效地使其磁化。磁化的间充质干细胞能正常分化为成骨细胞和脂肪细胞。此外，非磁化的间充质干细胞和磁化的间充质干细胞通过旁分泌作用，增加了C2C12小鼠骨骼肌肌管中白细胞介素 - 6（IL - 6）和诱导型一氧化氮合酶mRNA的表达，并降低了肿瘤坏死因子 - α（TNF - α）和白细胞介素 - 1β（IL - 1β）mRNA的表达。而且，在磁场存在的情况下，局部注射后磁化的间充质干细胞在细胞培养板和小鼠骨骼肌中显著留存。此外，磁化的间充质干细胞显著增加了发炎骨骼肌中白细胞介素 - 6（IL - 6）和白细胞介素 - 10（IL - 10）mRNA的表达，并降低了肿瘤坏死因子 - α（TNF - α）和白细胞介素 - 1β（IL - 1β）mRNA的表达。这些结果表明，磁化的间充质干细胞可能对有效的肌肉减少症治疗有用。
Sarcopenia, an age-related reduction in skeletal muscle mass and strength, is mainly caused by chronic inflammation. Because mesenchymal stem cells (MSCs) have the capacity to both promote myogenic cell differentiation and suppress inflammation, they are a promising candidate for sarcopenia treatment. In this study, to achieve the long-term retention of MSCs in skeletal muscle, we prepared magnetized MSCs using magnetic anionic liposome/atelocollagen complexes that we had previously developed, and evaluated their retention efficiency and immunomodulatory effects in mouse inflamed skeletal muscle. Mouse MSCs were efficiently magnetized by incubation with magnetic anionic liposome/atelocollagen complexes for 30 min under a magnetic field. The magnetized MSCs differentiated normally into osteoblasts and adipocytes. Additionally, nonmagnetized MSCs and magnetized MSCs increased IL-6 and inducible nitric oxide synthase mRNA expression and decreased TNF-alpha and IL-1 beta mRNA expression in C2C12 mouse skeletal muscle myotubes through paracrine effects. Moreover, magnetized MSCs were significantly retained in cell culture plates and mouse skeletal muscle after their local injection in the presence of a magnetic field. Furthermore, magnetized MSCs significantly increased IL-6 and IL-10 mRNA expression and decreased TNF-alpha and IL-1 beta mRNA expression in inflamed skeletal muscle. These results suggest that magnetized MSCs may be useful for effective sarcopenia treatment.