Department of Biochemistry and Molecular Biology, Department of Physiology and Biomedical Engineering, Mayo Clinic, Jacksonville, FL, 32224, USA.
Department of Surgery, Surgical Lab, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.
Small. 2020 Mar;16(10):e1904064. doi: 10.1002/smll.201904064. Epub 2020 Feb 18.
Extracellular vesicles secreted from adipose-derived mesenchymal stem cells (ADSCs) have therapeutic effects in inflammatory diseases. However, production of extracellular vesicles (EVs) from ADSCs is costly, inefficient, and time consuming. The anti-inflammatory properties of adipose tissue-derived EVs and other biogenic nanoparticles have not been explored. In this study, biogenic nanoparticles are obtained directly from lipoaspirate, an easily accessible and abundant source of biological material. Compared to ADSC-EVs, lipoaspirate nanoparticles (Lipo-NPs) take less time to process (hours compared to months) and cost less to produce (clinical-grade cell culture facilities are not required). The physicochemical characteristics and anti-inflammatory properties of Lipo-NPs are evaluated and compared to those of patient-matched ADSC-EVs. Moreover, guanabenz loading in Lipo-NPs is evaluated for enhanced anti-inflammatory effects. Apolipoprotein E and glycerolipids are enriched in Lipo-NPs compared to ADSC-EVs. Additionally, the uptake of Lipo-NPs in hepatocytes and macrophages is higher. Lipo-NPs and ADSC-EVs have comparable protective and anti-inflammatory effects. Specifically, Lipo-NPs reduce toll-like receptor 4-induced secretion of inflammatory cytokines in macrophages. Guanabenz-loaded Lipo-NPs further suppress inflammatory pathways, suggesting that this combination therapy can have promising applications for inflammatory diseases.
脂肪间充质干细胞（ADSCs）分泌的细胞外囊泡在炎症性疾病中有治疗作用。然而，从 ADSC 中产生细胞外囊泡（EVs）既昂贵又低效且耗时。脂肪组织来源的 EVs 和其他生物源纳米颗粒的抗炎特性尚未得到探索。在这项研究中，生物源纳米颗粒直接从脂肪抽吸物中获得，脂肪抽吸物是一种容易获得且丰富的生物材料来源。与 ADSC-EVs 相比，脂肪抽吸物纳米颗粒（Lipo-NPs）的处理时间更短（需要数小时，而不是数月），生产成本更低（不需要临床级别的细胞培养设施）。评估了 Lipo-NPs 的理化特性和抗炎特性，并将其与患者匹配的 ADSC-EVs 进行了比较。此外，还评估了 Lipo-NPs 中胍那苄的载药量，以增强抗炎效果。与 ADSC-EVs 相比，Lipo-NPs 富含载脂蛋白 E 和甘油脂质。此外，肝细胞和巨噬细胞对 Lipo-NPs 的摄取量更高。Lipo-NPs 和 ADSC-EVs 具有相当的保护和抗炎作用。具体来说，Lipo-NPs 可减少巨噬细胞中 TLR4 诱导的炎症细胞因子的分泌。载胍那苄的 Lipo-NPs 进一步抑制炎症途径，表明这种联合治疗可能对炎症性疾病有很好的应用前景。
