Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Bern, 3012, Switzerland.
Functional Genomics Center Zurich (FGCZ), University of Zurich/ETH Zurich, Zurich, 8057, Switzerland.
Adv Healthc Mater. 2023 Dec;12(30):e2300811. doi: 10.1002/adhm.202300811. Epub 2023 Sep 17.
A new therapeutic approach using cell-derived nanovesicles (cdNVs) is offered here to overcome the lack of effective treatments for liver fibrosis, a reversible chronic liver disease. To achieve this goal the formation and purification of cdNVs from untreated, quiescent-like, or activated LX-2 cells, an immortalized human hepatic stellate cell (HSC) line with key features of transdifferentiated HSCs are established. Analysis of the genotype and phenotype of naïve and transdifferentiated LX-2 cells activated through transforming growth factor beta 1, following treatment with cdNVs, reveals a concentration-dependent fibrosis regression. The beneficial fibrosis-resolving effects of cdNVs are linked to their biomolecular corona. Liposomes generated using lipids extracted from cdNVs exhibit a reduced antifibrotic response in perpetuated LX-2 cells and show a reduced cellular uptake. However, incubation with soluble factors collected during purification results in a new corona, thereby restoring fibrosis regression activity. Overall, cdNVs display encouraging therapeutic properties, making them a promising candidate for the development of liver fibrosis resolving therapeutics.
这里提供了一种新的治疗方法，即使用细胞衍生的纳米囊泡（cdNVs），以克服肝纤维化（一种可逆转的慢性肝病）缺乏有效治疗方法的问题。为了实现这一目标，从未经处理的、静止样的或激活的 LX-2 细胞中建立了 cdNVs 的形成和纯化方法，LX-2 细胞是一种永生化的人肝星状细胞（HSC）系，具有转分化 HSC 的关键特征。分析经过转化生长因子β 1 处理后，使用 cdNVs 处理的原始和转分化的 LX-2 细胞的基因型和表型，显示出浓度依赖性的纤维化消退。cdNVs 的有益纤维化消退作用与其生物分子冠有关。使用从 cdNVs 中提取的脂质生成的脂质体在持续的 LX-2 细胞中显示出较低的抗纤维化反应，并表现出较低的细胞摄取。然而，与在纯化过程中收集的可溶性因子孵育会产生新的冠，从而恢复纤维化消退活性。总体而言，cdNVs 显示出令人鼓舞的治疗特性，使它们成为开发肝纤维化消退治疗的有前途的候选物。
