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bioRxiv · 10.1101/172213

Regulation of mesenchymal stem cell function by TGFβ-1 on mast cell extracellular vesicles -- role of endosomal retention

Yin, Y.·Shelke, G. V.·Jang, S. C.·Lasser, C.·Wennmalm, S.·Hoffmann, H. J.·Nilsson, J.·Li, L.·Gho, Y. S.·Lotvall, J.
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Abstract

Extracellular vesicles (EVs) convey biological messages between cells, either by surface-to-surface interaction, or by shuttling of bioactive molecules to a recipient cell cytoplasm. Here we show that EVs released by human primary mast cells or transformed human mast cells (HMC1), carry TGF{beta}-1 on their surface. EV-associated TGF{beta}-1 enhance the migratory activity of human mesenchymal stem cells (MSCs) compared to free TGF{beta}-1, as both knockdown of TGF{beta}, or a TGF{beta}-antibody, attenuate the effect. The MSCs respond by increasing matrix metalloproteinase-2 and -9 (MMP) activity. Further, EVs given to MSCs are retained in the endosomal compartments at a time of biological function, prolonging EV-associated TGF{beta}-1 signaling vs free TGF{beta}-1. When exposed to EVs, MSCs home more toward allergen-exposed lung in a mouse allergen model, resulting in attenuated allergic inflammation. Our results show that mast cell-EVs are decorated with TGFb-1, are retained in endosomes, which influences both MSC phenotype and function.

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Yin, Y., Shelke, G. V., Jang, S. C., Lasser, C., Wennmalm, S., Hoffmann, H. J., Nilsson, J., Li, L., Gho, Y. S., Lotvall, J.. 2017-08-04. Regulation of mesenchymal stem cell function by TGFβ-1 on mast cell extracellular vesicles -- role of endosomal retention. https://doi.org/10.1101/172213

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