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利用磁性脂质体对间充质干细胞进行磁化可增强其在小鼠炎症性骨骼肌中的保留和免疫调节功效。

Magnetization of mesenchymal stem cells using magnetic liposomes enhances their retention and immunomodulatory efficacy in mouse inflamed skeletal muscle.

机构信息

Ritsumeikan-Global Innovation Research Organization, Ritsumeikan University, 1-1-1 Noji-Higashi, Kusatsu 525-8577, Japan.

Ritsumeikan-Global Innovation Research Organization, Ritsumeikan University, 1-1-1 Noji-Higashi, Kusatsu 525-8577, Japan; Faculty of Sport and Health Science, Ritsumeikan University, 1-1-1 Noji-Higashi, Kusatsu 525-8577, Japan.

出版信息

Int J Pharm. 2021 Mar 1;596:120298. doi: 10.1016/j.ijpharm.2021.120298. Epub 2021 Jan 30.

Abstract

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, non-magnetized MSCs and magnetized MSCs increased IL-6 and inducible nitric oxide synthase mRNA expression and decreased TNF-α and IL-1β 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-α and IL-1β mRNA expression in inflamed skeletal muscle. These results suggest that magnetized MSCs may be useful for effective sarcopenia treatment.

摘要

肌肉减少症是一种与年龄相关的骨骼肌质量和力量下降,主要由慢性炎症引起。间充质干细胞(MSCs)具有促进肌源性细胞分化和抑制炎症的能力,因此是肌肉减少症治疗的有前途的候选物。在这项研究中,为了实现 MSCs 在骨骼肌中的长期保留,我们使用我们之前开发的带负电荷的磁性阴离子脂质体/胶原复合物来制备磁化 MSCs,并评估它们在小鼠炎症性骨骼肌中的保留效率和免疫调节作用。将 MSC 在磁场下与带负电荷的磁性阴离子脂质体/胶原复合物孵育 30 分钟,可有效地将 MSC 磁化。磁化的 MSC 可正常分化为成骨细胞和成脂细胞。此外,通过旁分泌作用,非磁化 MSC 和磁化 MSC 增加 C2C12 小鼠骨骼肌肌管中的 IL-6 和诱导型一氧化氮合酶 mRNA 表达,并降低 TNF-α 和 IL-1β mRNA 表达。此外,在磁场存在下局部注射后,磁化 MSC 可在细胞培养板和小鼠骨骼肌中得到显著保留。此外,磁化 MSC 可显著增加炎症性骨骼肌中的 IL-6 和 IL-10 mRNA 表达,并降低 TNF-α 和 IL-1β mRNA 表达。这些结果表明,磁化 MSC 可能对有效的肌肉减少症治疗有用。

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