The metabolic syndrome modifies the mRNA expression profile of extracellular vesicles derived from porcine mesenchymal stem cells

Yu Meng, Alfonso Eirin, Xiang Yang Zhu, Daniel R. O'Brien, Amir Lerman, Andre J. Van Wijnen, Lilach O. Lerman

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Background: Mesenchymal stem cells (MSCs) perform paracrine functions by releasing extracellular vesicles (EVs) containing microRNA, mRNA, and proteins. We investigated the mRNA content of EVs in metabolic syndrome (MetS) and tested hypothesis that comorbidities interfere with the paracrine functionality of MSCs. Methods: Mesenchymal stem cells were collected from swine abdominal adipose tissue after 16 weeks of a low- (Lean) or high-calorie (MetS) diet (n = 5 each). We used next-generation mRNAs sequencing to identify mRNAs enriched and depleted in Lean- or MetS-EVs compared to the parent MSCs. Results: We found 88 and 130 mRNAs enriched in Lean-EVs and MetS-EVs, respectively, of which only eight were common genes encoding proteins related to the nucleus, endoplasmic reticulum, and membrane fraction. Lean-EVs were enriched with mRNAs primarily involved in transcription regulation and the transforming growth factor (TGF)-β signaling pathway, but devoid of genes related to regulation of inflammation. In contrast, MetS-EVs contained mRNAs involved in translational regulation and modulation of inflammation mediated by chemokines and cytokines, but lacked mRNAs related to TGF-β signaling. mRNAs enriched in EVs have the potential to target a significant proportion of genes enriched in EVs, but only 4% microRNA target genes overlap between Lean- and MetS-EVs. Co-culture with MetS-EVs also increased renal tubular cell inflammation in-vitro. Conclusions: Metabolic syndrome may affect immunomodulatory function of porcine MSCs by modifying mRNA profiles of the EVs that they produce and post-transcriptional regulation. These observations may have important implications for cell-based therapy, and support development of strategies to improve the efficacy of MSCs and their EVs.

Original languageEnglish (US)
Article number58
JournalDiabetology and Metabolic Syndrome
Volume10
Issue number1
DOIs
StatePublished - Jul 21 2018

Keywords

  • Extracellular vesicles
  • Mesenchymal stem cells
  • Metabolic syndrome
  • Swine
  • mRNA

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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