Distinct targeting and uptake of platelet and red blood cell-derived extracellular vesicles into immune cells

Petra Ilvonen, Reetta Pusa, Kai Härkönen, Saara Laitinen, Ulla Impola
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Abstract

Blood-derived extracellular vesicles (EVs) hold great therapeutic potential. As blood contains mixed EV populations, it is challenging to study EVs originating from different cells separately. Blood cell concentrates manufactured in blood banks offer an excellent non-invasive source of blood cell-specific EV populations. To study blood cell-specific EVs, we isolated EVs from platelet (TREVs) and red blood cell (EryEVs) concentrates and characterized them using nanoparticle tracking analysis, imaging flow cytometry, electron microscopy and western blot analysis and co-cultured them with peripheral blood mononuclear cells (PBMCs). Our aim was to use imaging flow cytometry to investigate EV interaction with PBMCs as well as study their effects on T-lymphocyte populations to better understand their possible biological functions. As a conclusion, TREVs interacted with PBMCs more than EryEVs. Distinctively, TREVs were uptaken into CD11c+ monocytes rapidly and into CD19+ B-lymphocytes in 24 h. EryEVs were not uptaken into CD11c+ monocytes before the 24-h time point, and they were only seen on the surface of lymphocytes. Neither TREVs nor EryEV were uptaken into CD3+ T-lymphocytes and no effect on T-cell populations was detected. We have previously seen similar differences in targeting PC-3 cancer cells. Further studies are needed to address the functional properties of blood cell concentrate-derived EVs. This study demonstrates that imaging flow cytometry can be used to study the distinctive differences in the interaction and uptake of EVs. Considering our current and previous results, EVs present a new valuable component for the future development of blood-derived therapeutics.

Abstract Image

免疫细胞对血小板和红细胞衍生的胞外囊泡的不同靶向和摄取
源自血液的细胞外囊泡 (EV) 具有巨大的治疗潜力。由于血液中含有混合的 EV 群,要分别研究来自不同细胞的 EVs 具有挑战性。血库制造的血细胞浓缩物是血细胞特异性EV群的绝佳非侵入性来源。为了研究血细胞特异性 EVs,我们从血小板(TREVs)和红细胞(EryEVs)浓缩物中分离了 EVs,并使用纳米粒子追踪分析、成像流式细胞术、电子显微镜和 Western 印迹分析对其进行了表征,然后将它们与外周血单核细胞(PBMCs)共培养。我们的目的是利用成像流式细胞术研究 EV 与 PBMC 的相互作用,并研究它们对 T 淋巴细胞群的影响,从而更好地了解它们可能具有的生物功能。结论是,TREV 与 PBMC 的相互作用比 EryEV 更大。不同的是,TREVs 能迅速被 CD11c+ 单核细胞吸收,并在 24 小时内被 CD19+ B 淋巴细胞吸收。TREVs 和 EryEV 均未被 CD3+ T 淋巴细胞吸收,也未检测到对 T 细胞群的影响。我们之前在靶向 PC-3 癌细胞时也发现了类似的差异。要了解血细胞浓缩物衍生 EV 的功能特性,还需要进一步的研究。这项研究表明,成像流式细胞术可用于研究 EVs 相互作用和吸收的独特差异。考虑到我们目前和以前的研究结果,EVs 为未来血液衍生疗法的开发提供了一种新的有价值的成分。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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