PXD017413 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Transplantation of Telomerase/Myocardin Co-Expressing Mesenchymal Cells Promotes Revascularization and Tissue Repair in Murine Myocardial Infarction |
Description | Rationale and Objectives: Cellular therapies are hampered by poor survival and growth of grafts. We recently showed that the survival and repairing capacity of transplanted adult cells may be improved by co-expression of the anti-senescence telomerase reverse transcriptase (TERT) and anti-apoptotic myocardin (MYOCD). The current study aimed at testing whether forced co-expression of TERT and MYOCD improves post-infarct revascularization and tissue repair by adipose tissue-derived mesenchymal stromal cells (AT-MSCs). Methods: We transplanted AT-MSCs engineered to overexpress MYOCD and TERT in a murine model of acute myocardial infarction (AMI). We analyzed the immunoregulatory properties of AT-MSCs on post-AMI. We characterized in vitro and in vivo paracrine effects of AT-MSCs and their interactions with murine cardiospheres (CSps), all as parts of their reparative repertoire. Results: When transplanted into infarcted hearts of C57BL/6 mice, “rejuvenated” AT-MSCs overexpressing TERT and MYOCD (rAT-MSCs) decreased fibrosis and the intrafibrotic CD3 and B220 lymphocyte infiltration, and increased arteriolar density as well as ejection fraction compared with saline or mock-transduced AT-MSCs. These effects were accompanied by increased numbers of Ki-67+ and CD117+ cells, and the expression of cardiac actin and β-myosin heavy chain within the infarcted hearts. Both rAT-MSCs and their conditioned medium (CM) stimulated intracellular Ca2+ flux in CSps. CSp-derived cells had increased survival when preconditioned with CM or exosome-enriched fraction (Exo+) from rAT-MSCs and then exposed to simulated ischemia/reperfusion. Proteomic analysis of rAT-MSCs-Exo+ predicted the activation of vascular development and the inhibition of immune cell trafficking. Elevated concentration of miR-320a, miR-150-5p and miR-126-3p associated with regulation of apoptosis and vasculogenesis was confirmed in rAT-MSCs-Exo+. Conclusions: rAT-MSCs promote vasculogenesis and cell survival and reduce post-AMI inflammatory responses in a murine model of AMI. An integrated experimental and computational analysis revealed that Exo+ is the active component of the paracrine secretion by rAT-MSCs, with pro-angiogenic and pro-survival activities. |
HostingRepository | PRIDE |
AnnounceDate | 2020-12-02 |
AnnouncementXML | Submission_2020-12-02_04:13:39.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Piero Del Boccio |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | iodoacetamide derivatized residue |
Instrument | maXis |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-02-06 03:44:31 | ID requested | |
⏵ 1 | 2020-12-02 04:13:39 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: adipose tissue–derived mesenchymal stromal cells |
telomerase |
myocardin |
myocardial infarction, exosomes, extracellular vesicles. |
Contact List
Piero Del Boccio |
contact affiliation | University of Chieti-Pescara, Depatment of Pharmacy |
contact email | piero.delboccio@unich.it |
lab head | |
Piero Del Boccio |
contact affiliation | University "G. d'Annunzio" of Chieti-Pescara |
contact email | piero.delboccio@unich.it |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD017413
- Label: PRIDE project
- Name: Transplantation of Telomerase/Myocardin Co-Expressing Mesenchymal Cells Promotes Revascularization and Tissue Repair in Murine Myocardial Infarction