PXD032744

PXD032744 is an original dataset announced via ProteomeXchange.

Title	Independent human mesenchymal stromal cell-derived extracellular vesicle preparations differentially attenuate symptoms in an advanced murine Graft-versus-Host-Disease model
Description	Extracellular vesicles (EVs) harvested from conditioned media of human mesenchymal stromal cells (MSCs) suppress acute inflammation in various disease models and promote regeneration of damaged tissues. Following successful treatment of an acute steroid-refractory Graft-versus-Host disease (GvHD) patient with EVs prepared from conditioned media of human bone marrow-derived MSCs, we focus on improving the MSC-EV production for the clinical application. Independent MSC-EV preparations all produced according to a standardized procedure, reveal broad immunomodulatory differences. Only a proportion of our MSC-EV products effectively modulate immune responses in a multi-donor mixed lymphocyte reaction (mdMLR) assay. To explore the relevance of such differences, we have established an optimized mouse GvHD model. The functional testing of selected MSC-EV preparations demonstrate that MSC-EV preparations revealing immunomodulatory capabilities in the mdMLR assay also effectively suppress GvHD symptoms in this model. In contrast, MSC-EV preparations, lacking such in vitro activities, also fail to modulate GvHD symptoms in vivo. Searching for differences of the active and inactive MSC-EV preparations, we failed to identify concrete proteins or miRNAs that could serve as surrogate markers. Thus, standardized MSC-EV production strategies may not be sufficient to warrant manufacturing of MSC-EV products with reproducible qualities. Consequently, given this functional heterogeneity, every individual MSC-EV preparation considered for the clinical application should be evaluated for its therapeutic potency prior to administration to patients. Here, we qualified the mdMLR assay for such analyses.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:00:47.893.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Frank Stein
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-23 07:31:10	ID requested
1	2023-06-12 09:22:13	announced
⏵ 2	2023-11-14 09:00:56	announced	2023-11-14: Updated project metadata.

Madel RJ, B, ö, rger V, Dittrich R, Bremer M, Tertel T, Phuong NNT, Baba HA, Kordelas L, Staubach S, Stein F, Haberkant P, Hackl M, Grillari R, Grillari J, Buer J, Horn PA, Westendorf AM, Brandau S, Kirschning CJ, Giebel B, Independent human mesenchymal stromal cell-derived extracellular vesicle preparations differentially attenuate symptoms in an advanced murine graft-versus-host disease model. Cytotherapy, 25(8):821-836(2023) [pubmed]

submitter keyword: exosomes, Graft-versus-Host Disease,mesenchymal stem cells, extracellular vesicles, heterogeneity, mesenchymal stromal cells

Prof. Dr. Bernd Giebel
contact affiliation	University Hospital Essen (AöR) Institute for Transfusionmedicine Virchowstr. 179 D-45147 Essen
contact email	Bernd.giebel@uk-essen.de
lab head
Frank Stein
contact affiliation	EMBL
contact email	frank.stein@embl.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/06/PXD032744

PRIDE project URI

• PRIDE
  1. PXD032744
     1. Label: PRIDE project
     2. Name: Independent human mesenchymal stromal cell-derived extracellular vesicle preparations differentially attenuate symptoms in an advanced murine Graft-versus-Host-Disease model