PDF(Pubmed)
Abstract：
Extracellular vesicles (EVs) secreted by stem and progenitor cells have significant potential as cell-free \'cellular\' therapeutics. Yet, small EVs (<200 nm) are rapidly cleared after systemic administration, mainly by the liver, presenting challenges targeting EVs to a specific organ or tissue. Microencapsulation using natural nano-porous hydrogels (microgels) has been shown to enhance engraftment and increase the survival of transplanted cells. We sought to encapsulate EVs within microgels to target their delivery to the lung by virtue of their size-based retention within the pulmonary microcirculation. Mesenchymal stromal cell (MSC) derived EVs were labelled with the lipophilic dye (DiR) and encapsulated within agarose-gelatin microgels. Endothelial cells and bone marrow derived macrophages were able to take up EVs encapsulated in microgels in vitro, but less efficiently than the uptake of free EVs. Following intrajugular administration, microgel encapsulated EVs were selectively retained within the lungs for 72h, while free EVs were rapidly cleared by the liver. Furthermore, microgel-loaded EVs demonstrated greater uptake by lung cells, in particular CD45+ immune cells, as assessed by flow cytometry compared to free EVs. Microencapsulation of EVs may be a novel tool for enhancing the targeted delivery of EVs for future therapeutic applications.
摘要：
干细胞和祖细胞分泌的细胞外囊泡(EV)具有作为无细胞“细胞”疗法的巨大潜力。然而，小电动汽车（<200nm）在全身给药后迅速清除，主要是肝脏，针对特定器官或组织的电动汽车提出了挑战。已显示使用天然纳米多孔水凝胶(微凝胶)的微囊化增强植入并增加移植细胞的存活。我们试图将EV封装在微凝胶内，以凭借其在肺微循环内的基于大小的保留将其递送到肺。间充质基质细胞（MSC）衍生的EV用亲脂性染料（DiR）标记，并封装在琼脂糖明胶微凝胶中。内皮细胞和骨髓来源的巨噬细胞能够在体外吸收包裹在微凝胶中的电动汽车，但效率低于游离电动汽车的吸收。颈内给药后，微凝胶包封的电动汽车选择性地保留在肺内72小时，而游离的电动汽车被肝脏迅速清除。此外，负载微凝胶的电动汽车表现出更大的肺细胞摄取，特别是CD45+免疫细胞，通过流式细胞术评估，与游离电动汽车相比。EV的微囊化可能是用于增强EV的靶向递送以用于未来治疗应用的新工具。
