Dataset Information

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

ABSTRACT: Allogeneic regenerative cell therapy has shown surprising results despite lack of engraftment of the transplanted cells. Their efficacy was so far considered to be mostly due to secreted trophic factors. We hypothesized that extracellular vesicles (EVs) can also contribute to their mode of action. Here we provide evidence that EVs derived from therapeutic placental-expanded (PLX) stromal cells are potent inducers of angiogenesis and modulate immune cell proliferation in a dose dependent manner. Crude EVs were enriched >100-fold from large volume PLX conditioned media via tangential flow filtration (TFF) as determined by tunable resistive pulse sensing (TRPS). Additional TFF purification was devised to separate EVs from cell-secreted soluble factors. EV identity was confirmed by western blot, calcein-based flow cytometry and electron microscopy. Surface marker profiling of tetraspanin-positive EVs identified expression of cell- and matrix-interacting adhesion molecules. Quantitative proteomics using isobaric labeling comparing PLX-EVs to PLX-derived soluble factors revealed significant differential enrichment of 495 proteins in purified PLX-EVs involved in angiogenesis, cell movement and immune system signaling. At the functional level, PLX-EVs and cells but not the corresponding soluble factors inhibited T cell mitogenesis. PLX-EVs and soluble factors displayed dose-dependent proangiogenic potential by enhancing tube-like structure formation in vitro. Our findings indicate an alternative mode of PLX action based on EV-mediated proangiogenic function and immune response modulation that may help explaining clinical efficacy beyond presence of the transplanted allogeneic cells.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Placenta, Cell Culture

SUBMITTER: Constantin Blöchl

LAB HEAD: Christian G. Huber

PROVIDER: PXD014572 | Pride | 2022-05-19

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	20190227_CoB_PepMap100_H5M9_PLX_PMU_aMEM_HPL_unlabeled_010.raw	Raw
	20190227_CoB_PepMap100_H5M9_PLX_PMU_crude_15_unlabeled_001.raw	Raw
	20190227_CoB_PepMap100_H5M9_PLX_PMU_crude_25_unlabeled_004.raw	Raw
	20190227_CoB_PepMap100_H5M9_PLX_PMU_crude_27_unlabeled_007.raw	Raw
	20190227_CoB_PepMap100_H5M9_PLX_PMU_pur_15_unlabeled_002.raw	Raw

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Publications

A functional corona around extracellular vesicles enhances angiogenesis, skin regeneration and immunomodulation.

Wolf Martin M Poupardin Rodolphe W RW Ebner-Peking Patricia P Andrade André Cronemberger AC Blöchl Constantin C Obermayer Astrid A Gomes Fausto Gueths FG Vari Balazs B Maeding Nicole N Eminger Essi E Binder Heide-Marie HM Raninger Anna M AM Hochmann Sarah S Brachtl Gabriele G Spittler Andreas A Heuser Thomas T Ofir Racheli R Huber Christian G CG Aberman Zami Z Schallmoser Katharina K Volk Hans-Dieter HD Strunk Dirk D

Journal of extracellular vesicles 20220401 4

Nanoparticles can acquire a plasma protein corona defining their biological identity. Corona functions were previously considered for cell-derived extracellular vesicles (EVs). Here we demonstrate that nano-sized 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 (TFF) and subtractive tande ...[more]

PMID: 35398993

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