PXD014572

PXD014572 is an original dataset announced via ProteomeXchange.

Title	Extracellular vesicles from therapeutic grade allogeneic human placental stromal cells induce angiogenesis and modulate immunity
Description	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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:36:24.629.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Constantin Blöchl
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2019-07-11 07:17:55	ID requested
1	2022-05-19 03:30:29	announced
⏵ 2	2024-10-22 05:36:25	announced	2024-10-22: Updated project metadata.

Wolf M, Poupardin RW, Ebner-Peking P, Andrade AC, Bl, ö, chl C, Obermayer A, Gomes FG, Vari B, Maeding N, Eminger E, Binder HM, Raninger AM, Hochmann S, Brachtl G, Spittler A, Heuser T, Ofir R, Huber CG, Aberman Z, Schallmoser K, Volk HD, Strunk D, A functional corona around extracellular vesicles enhances angiogenesis, skin regeneration and immunomodulation. J Extracell Vesicles, 11(4):e12207(2022) [pubmed]

10.1002/jev2.12207;

curator keyword: Biological

submitter keyword: PLX stromal cells, EV, Cell Therapy, TFF, TRPS, PAD, CLI

Christian G. Huber
contact affiliation	Department of Biosciences, University of Salzburg
contact email	c.huber@sbg.ac.at
lab head
Constantin Blöchl
contact affiliation	Department of Biosciences, University of Salzburg
contact email	constantin.bloechl@sbg.ac.at
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD014572
     1. Label: PRIDE project
     2. Name: Extracellular vesicles from therapeutic grade allogeneic human placental stromal cells induce angiogenesis and modulate immunity