Katsuda Takeshi, Oki Katsuyuki, Ochiya Takahiro
Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Methods Mol Biol. 2015;1212:171-81. doi: 10.1007/7651_2014_98.
In the last 20 years, extracellular vesicles (EVs) have attracted attention as a versatile cell-cell communication mediator. The biological significance of EVs remains to be fully elucidated, but many reports have suggested that the functions of EVs mirror, at least in part, those of the cells from which they originate. Mesenchymal stem cells (MSCs) are a type of adult stem cell that can be isolated from connective tissue including bone marrow and adipose tissue and have emerged as an attractive candidate for cell therapy applications. Accordingly, an increasing number of reports have shown that EVs derived from MSCs have therapeutic potential in multiple diseases. We recently reported a novel therapeutic potential of EVs secreted from human adipose tissue-derived MSCs (hADSCs) (also known as adipose tissue-derived stem cells; ASCs) against Alzheimer's disease (AD). We found that hADSCs secrete exosomes carrying enzymatically active neprilysin, the most important β-amyloid peptide (Aβ)-degrading enzyme in the brain. In this chapter, we describe a method by which to evaluate the therapeutic potential of hADSC-derived EVs against AD from the point of view of their Aβ-degrading capacity.
在过去20年中,细胞外囊泡(EVs)作为一种多功能的细胞间通讯介质受到了关注。EVs的生物学意义仍有待充分阐明,但许多报告表明,EVs的功能至少部分反映了其来源细胞的功能。间充质干细胞(MSCs)是一种成体干细胞,可从包括骨髓和脂肪组织在内的结缔组织中分离出来,已成为细胞治疗应用中颇具吸引力的候选者。因此,越来越多的报告表明,源自MSCs的EVs在多种疾病中具有治疗潜力。我们最近报道了人脂肪组织来源的间充质干细胞(hADSCs,也称为脂肪组织来源的干细胞;ASCs)分泌的EVs对阿尔茨海默病(AD)具有新的治疗潜力。我们发现hADSCs分泌携带酶活性中性内肽酶的外泌体,中性内肽酶是大脑中最重要的β-淀粉样肽(Aβ)降解酶。在本章中,我们描述了一种从hADSC来源的EVs降解Aβ的能力角度评估其对AD治疗潜力的方法。