Unknown,Transcriptomics,Genomics,Proteomics

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Microarray analysis of differences in miRNA expression between human mesenchymal stem cells isolated from olfactory mucosa and bone

ABSTRACT: This experiment investigates differences in miRNA expression between different populations of human mesenchymal stem cells (MSCs), which are a potential treatment for multiple sclerosis (MS). Previously it has been reported that MSCs derived from human olfactory mucosa (OM-MSCs) may be a better candidate for the treatment of MS than MSCs derived from bone marrow (BM-MSCs), due to a better ability to promote CNS myelination in vitro. In this study, miRNA profiling of OM-MSCs and BM-MSCs was undertaken to investigate the differences between these two cell types in relation to their prospective therapeutic use.

ORGANISM(S): Homo sapiens

SUBMITTER: David Mallinson

PROVIDER: E-MTAB-4594 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project 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.

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Microarray analysis of differences in miRNA expression between human mesenchymal stem cells isolated from olfactory mucosa and bone

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