Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, GA, 30332, USA.
Department of Molecular Science and Technology, Ajou University, Suwon, 16499, South Korea.
Adv Biol (Weinh). 2024 Mar;8(3):e2300462. doi: 10.1002/adbi.202300462. Epub 2023 Dec 24.
Cell therapies involving c-kit+ progenitor cells (CPCs) and mesenchymal stem cells (MSCs) have been actively studied for cardiac repair. The benefits of such therapies have more recently been attributed to the release of small extracellular vesicles (sEVs) from the parent cells. These sEVs are 30-180 nm vesicles containing protein/nucleic acid cargo encapsulated within an amphiphilic bilayer membrane. Despite their pro-reparative effects, sEV composition and cargo loading is highly variable, making it challenging to develop robust therapies with sEVs. Synthetic alternatives have been developed to allow cargo modulation, including prior work from the laboratory, to design sEV-like vehicles (ELVs). ELVs are synthesized from the sEV membrane but allow controlled cargo loading. It is previously shown that loading pro-angiogenic miR-126 into CPC-derived ELVs significantly increases endothelial cell angiogenesis compared to CPC-sEVs alone. Here, they expand on this work to design MSC-derived ELVs and study the role of the parent cell type on ELV composition and function. It is found that ELV origin does affect the ELV potency and that ELV membrane composition can affect outcomes. This study showcases the versatility of ELVs to be synthesized from different parent cells and highlights the importance of selecting ELV source cells based on the desired functional outcomes.
细胞疗法涉及 c-kit+祖细胞 (CPCs) 和间充质干细胞 (MSCs),目前正在积极研究用于心脏修复。最近,这些疗法的益处归因于亲代细胞释放的小细胞外囊泡 (sEVs)。这些 sEVs 是 30-180nm 的囊泡,其中包含封装在两亲性双层膜中的蛋白质/核酸货物。尽管 sEV 具有促修复作用,但 sEV 的组成和货物装载高度可变,这使得使用 sEV 开发稳健的疗法具有挑战性。已经开发了合成替代品来允许货物调节,包括实验室之前的工作,以设计 sEV 样载体 (ELVs)。ELVs 是从 sEV 膜合成的,但允许控制货物装载。以前的研究表明,将促血管生成的 miR-126 加载到 CPC 衍生的 ELVs 中,与单独的 CPC-sEV 相比,显著增加了内皮细胞的血管生成。在这里,他们扩展了这项工作,设计了 MSC 衍生的 ELVs,并研究了亲代细胞类型对 ELV 组成和功能的影响。结果发现,ELV 的起源确实会影响 ELV 的效力,并且 ELV 膜组成会影响结果。这项研究展示了 ELVs 从不同的亲代细胞中合成的多功能性,并强调了根据预期的功能结果选择 ELV 源细胞的重要性。