Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.
State Key Laboratory of Medical Proteomics, National Chromatographic R. & A. Center, CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.
J Nanobiotechnology. 2024 Nov 10;22(1):686. doi: 10.1186/s12951-024-02956-w.
Extracellular vesicles (EVs) carry a variety of bioactive molecules and are becoming a promising alternative to cell therapy. Scale-up EV isolation is necessary for their functional studies and biological applications, while the traditional methods are challenged by low throughput, low yield, and potential damage. Herein, we developed an ion osmolarity-driven sequential concentration-enrichment strategy (IOSCE) for the EV isolation. IOSCE is composed of a novel superabsorbent polymers (SAPs) for EV concentration and a charged polymer for EV enrichment. Based on the driving force of ionic osmotic pressure, IOSCE can isolate EVs on a large scale from cell culture medium. The saturated water absorption capacity of IOSCE is 13.62 times higher than that of commercial SAPs. Compared with the ultracentrifugation method, IOSCE exhibited a 2.64 times higher yield (6.33 × 10 particles/mL). Moreover, the mesenchymal stem cell-derived EVs isolated using IOSCE demonstrate strong biological activity and can reduce neuroinflammation by affecting RNA metabolism and translation processes. IOSCE provides a cost-effective, high-throughput, and low-damage method for the scale up EV isolation, which is promising for disease diagnosis and treatment.
细胞外囊泡（EVs）携带多种生物活性分子，正在成为细胞治疗的一种有前途的替代方法。为了对其进行功能研究和生物应用，需要对 EV 进行大规模分离，但传统方法存在通量低、产量低和潜在损伤等问题。本研究开发了一种离子渗透压驱动的顺序浓缩-富集策略（IOSCE）用于 EV 分离。IOSCE 由新型超吸水性聚合物（SAPs）用于 EV 浓缩和带电荷聚合物用于 EV 富集组成。基于离子渗透压的驱动力，IOSCE 可以从细胞培养液中大规模分离 EV。IOSCE 的饱和水吸收能力比商业 SAPs 高 13.62 倍。与超速离心法相比，IOSCE 的产率高 2.64 倍（6.33×10^9 个颗粒/mL）。此外，使用 IOSCE 分离的间充质干细胞来源的 EV 具有很强的生物活性，可通过影响 RNA 代谢和翻译过程来减轻神经炎症。IOSCE 为 EV 的大规模分离提供了一种经济高效、高通量且低损伤的方法，有望用于疾病诊断和治疗。
