Department of Medicinal Biochemistry, School of Medicine, Aydin Adnan Menderes University, Aydin, Turkey.
Department of Pharmaceutical Technology, Faculty of Pharmacy, Acibadem University, Istanbul, Turkey.
PLoS One. 2022 Sep 15;17(9):e0274607. doi: 10.1371/journal.pone.0274607. eCollection 2022.
Mesenchymal stem cells can be obtained and multiplied from various sources and have a very high capacity to release exosomes. Exosomes are nano-sized extracellular vesicles containing biological signaling molecules. This study aimed to determine the effect of MSC-derived exosomes as a drug delivery system for paclitaxel in cervical cancer cells. In this study, human MSC were isolated from wharton jelly of umbilical cord tissue (WJ-MSC), and cells were characterized by CD44, CD90, CD105, and CD34 staining. Exosomes were released in WJ-MSC cells with serum-starved conditions for 48 hours, and particle sizes and structures were examined with zeta-sizer and TEM. In addition, exosomes CD9, CD63, and CD81 markers were checked by western blot. Paclitaxel was loaded into exosomes (Exo-PAC) by electroporation and then incubated with Hela cervical cancer cells for 24 hours. TGF-β, SMAD, Snail, Slug, β-catenin, Notch, Caspase-3, Caspase-9, Bax, Bcl-2 protein and gene expression levels were analyzed in Hela cells. As a result, low concentration Exo-PAC induced apoptosis, and suppressed epithelial-mesenchymal transition proteins in Hela cells. In this study, it has been demonstrated that WJ-MSCs can be used as drug delivery systems for cervical cancer if exosomes are produced scalably in the future.
间充质干细胞可以从各种来源中获得和扩增,并且具有非常高的释放外泌体的能力。外泌体是一种纳米大小的细胞外囊泡,其中含有生物信号分子。本研究旨在确定 MSC 衍生的外泌体作为紫杉醇在宫颈癌细胞中的药物递送系统的效果。在这项研究中,我们从脐带组织的华通氏胶(WJ-MSC)中分离出人 MSC,并通过 CD44、CD90、CD105 和 CD34 染色对细胞进行鉴定。在血清饥饿条件下将外泌体释放到 WJ-MSC 细胞中 48 小时,并用 zeta-sizer 和 TEM 检查颗粒大小和结构。此外,还通过 Western blot 检查外泌体 CD9、CD63 和 CD81 标志物。通过电穿孔将紫杉醇加载到外泌体(Exo-PAC)中,然后将其与 Hela 宫颈癌细胞共孵育 24 小时。分析了 Hela 细胞中的 TGF-β、SMAD、Snail、Slug、β-catenin、Notch、Caspase-3、Caspase-9、Bax、Bcl-2 蛋白和基因表达水平。结果表明,低浓度的 Exo-PAC 诱导 Hela 细胞凋亡,并抑制上皮-间充质转化蛋白。在这项研究中,如果未来能够规模化生产外泌体,那么 WJ-MSC 可以被用作宫颈癌的药物递送系统。