Extracellular vesicles from therapeutic grade allogeneic human placental stromal cells induce angiogenesis and modulate immunity

Wolf, m.; Vari, B.; Bloechl, C.; Raninger, A. M.; Poupardin, R.; Beez, C. M.; Hoog, A.; Brachtl, G.; Eminger, E.; Binder, H. M.; Oeller, M.; Spittler, A.; Heuser, T.; Obermayer, A.; Seifert, M.; Huber, C. G.; Schallmoser, K.; Volk, H. D.; Strunk, D.

doi:10.1101/808808

bioRxiv · 10.1101/808808

Extracellular vesicles from therapeutic grade allogeneic human placental stromal cells induce angiogenesis and modulate immunity

Wolf, m.·Vari, B.·Bloechl, C.·Raninger, A. M.·Poupardin, R.·Beez, C. M.·Hoog, A.·Brachtl, G.·Eminger, E.·Binder, H. M.·Oeller, M.·Spittler, A.·Heuser, T.·Obermayer, A.·Seifert, M.·Huber, C. G.·Schallmoser, K.·Volk, H. D.·Strunk, D.

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Abstract

Nanoparticles can acquire a protein corona defining their biological identity. Corona functions were not yet considered for cell-derived extracellular vesicles (EVs). Here we demonstrate that nanosized EVs from therapy-grade human placental-expanded (PLX) stromal cells are surrounded by an imageable and functional protein corona when enriched with permissive technology. Scalable EV separation from cell-secreted soluble factors via tangential flow-filtration and subtractive tandem mass-tag proteomics revealed significant enrichment of predominantly immunomodulatory and proangiogenic proteins. Western blot, calcein-based flow cytometry, super-resolution and electron microscopy verified EV identity. PLX-EVs protected corona proteins from protease digestion. EVs significantly ameliorated human skin regeneration and angiogenesis in vivo, induced differential signaling in immune cells, and dose-dependently inhibited T cell proliferation in vitro. Corona removal by size-exclusion or ultracentrifugation abrogated angiogenesis. Re-establishing an artificial corona by cloaking EVs with defined proangiogenic proteins served as a proof-of-concept. Understanding EV corona formation will improve rational EV-inspired nanotherapy design.

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Wolf, m., Vari, B., Bloechl, C., Raninger, A. M., Poupardin, R., Beez, C. M., Hoog, A., Brachtl, G., Eminger, E., Binder, H. M., Oeller, M., Spittler, A., Heuser, T., Obermayer, A., Seifert, M., Huber, C. G., Schallmoser, K., Volk, H. D., Strunk, D.. 2019-10-17. Extracellular vesicles from therapeutic grade allogeneic human placental stromal cells induce angiogenesis and modulate immunity. https://doi.org/10.1101/808808

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