Extracellular vesicles such as exosomes convey biological messages between cells, either by surface-to-surface interaction or by shuttling of bioactive molecules to a recipient cell’s cytoplasm. Here we show that exosomes released by mast cells harbour both active and latent transforming growth factor β-1 (TGFβ-1) on their surfaces. The latent form of TGFβ-1 is associated with the exosomes via heparinase-II and pH-sensitive elements. These vesicles traffic to the endocytic compartment of recipient human mesenchymal stem cells (MSCs) within 60 min of exposure. Further, the exosomes-associated TGFβ-1 is retained within the endosomal compartments at the time of signalling, which results in prolonged cellular signalling compared to free-TGFβ-1. These exosomes induce a migratory phenotype in primary MSCs involving SMAD-dependent pathways. Our results show that mast cell-derived exosomes are decorated with latent TGFβ-1 and are retained in recipient MSC endosomes, influencing recipient cell migratory phenotype. We conclude that exosomes can convey signalling within endosomes by delivering bioactive surface ligands to this intracellular compartment.

诸如外泌体的细胞外囊泡通过表面间相互作用或通过将生物活性分子穿梭到受体细胞的细胞质中而在细胞之间传递生物信息。在这里，我们显示肥大细胞释放的外泌体在其表面上同时具有活性和潜在转化生长因子β-1（TGFβ-1）。TGFβ-1的潜在形式通过肝素酶II和pH敏感元件与外泌体相关。这些囊泡在暴露后60分钟内流向受体人类间充质干细胞（MSC）的内吞室。此外，与外泌体相关的TGFβ-1在发信号时保留在内体区室中，与游离TGFβ-1相比，导致延长的细胞发信号。这些外泌体在涉及SMAD依赖性途径的原代MSC中诱导迁移表型。我们的结果表明，肥大细胞衍生的外泌体被潜在的TGFβ-1修饰，并保留在受体MSC内体中，影响受体细胞的迁移表型。我们得出的结论是，外来体可以通过将生物活性表面配体传递到该细胞内区室，从而在内体内传递信号。