PXD033253

PXD033253 is an original dataset announced via ProteomeXchange.

Title	CRISPR-Cas9 Editing of TLR4 Improves the Outcome of Cardiac Cell Therapy
Description	We developed and optimized a new electroporation protocol for CRISPR-Cas9 gene editing. This protocol achieved up to 68% success rate, when applied to isolated hMSCs from the heart and epicardial fat of patients with ischemic heart disease. While cell editing resulted lowered TLR4 expression in hMSCs, it did not affect classical markers of hMSCs and proliferation rate. Advanced protein mass spectrometry analysis revealed that edited cells secreted fewer proteins involved in inflammation and in extracellular matrix organization. The immunomodulatory effect of TLR4 editing was apparent in both free and EV-encapsulated proteins. Furthermore, edited cells expressed less NF-ƙB and secreted lower amounts of extracellular vesicles, pro-inflammatory and pro-fibrotic cytokines than unedited hMSCs. Cell therapy with edited and unedited hMSCs improved survival, left ventricular (LV) remodeling, and cardiac function after myocardial infarction (MI) in mice. Postmortem histologic analysis revealed clusters of edited cells that survived in the scar tissue 28 days after MI. Morphometric analysis showed that implantation of edited cells increased the area of myocardial islands in the scar tissue, reduced the occurrence of transmural scar, increased scar thickness, and markedly decreased expansion index, compared with unedited cells or saline.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:46:59.982.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tamar Ziv
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-14 05:44:16	ID requested
1	2023-05-10 13:47:04	announced
⏵ 2	2023-11-14 08:47:01	announced	2023-11-14: Updated project metadata.

Schary Y, Rotem I, Caller T, Lewis N, Shaihov-Teper O, Brzezinski RY, Lendengolts D, Raanani E, Sternik L, Naftali-Shani N, Leor J, CRISPR-Cas9 editing of TLR4 to improve the outcome of cardiac cell therapy. Sci Rep, 13(1):4481(2023) [pubmed]

submitter keyword: TLR4, cell therapy,mesenchymal stromal cells

Jonathan Leor
contact affiliation	Neufeld and Tamman Cardiovascular Research Institutes, Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Israel.
contact email	leorj@tauex.tau.ac.il
lab head
Tamar Ziv
contact affiliation	Technion
contact email	tamarz@technion.ac.il
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/2023/05/PXD033253

PRIDE project URI

• PRIDE
  1. PXD033253
     1. Label: PRIDE project
     2. Name: CRISPR-Cas9 Editing of TLR4 Improves the Outcome of Cardiac Cell Therapy