PXD017413

PXD017413 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2020-02-06 03:44:31	ID requested
⏵ 1	2020-12-02 04:13:39	announced

Dataset with its publication pending

submitter keyword: adipose tissue–derived mesenchymal stromal cells

telomerase

myocardin

myocardial infarction, exosomes, extracellular vesicles.

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

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PRIDE project URI

• PRIDE
  1. PXD017413
     1. Label: PRIDE project
     2. Name: Transplantation of Telomerase/Myocardin Co-Expressing Mesenchymal Cells Promotes Revascularization and Tissue Repair in Murine Myocardial Infarction