Background
Autologous transplantation of mesenchymal stem cells (MSCs) may be a viable option for the treatment of several diseases. Evidence indicates that MSCs release extracellular vesicles (EVs) that shuttle miRNAs to damaged parenchymal cells, activating an endogenous repair program. However, whether comorbidities, such as metabolic syndrome (MetS) interfere with the packaging of cargo of MSC-derived EVs has never been explored. We hypothesized that MetS modulates the miRNA content packed within MSC-derived EVs.
Methods
MSCs were collected from swine abdominal adipose tissue after 16 weeks of Lean or Obese diet (n=7 each). Next-generation miRNA sequencing (miRNA-seq) was performed to identify miRNAs enriched in MSC-derived EVs, and their predicted target genes. Functional pathway analysis of the top 50 target genes of the top 4 miRNAs enriched in each group was performed using FunRich.
Results
Fourteen and 8 miRNAs were enriched in Lean- and MetS- EVs, respectively. Target genes of miRNAs enriched in MetS-EVs were implicated in the development of MetS and its complications, including diabetes-related pathways, validated transcriptional targets of AP1 family members Fra1 and Fra2, Class A/1 (Rhodopsin-like receptors), and Peptide ligand-binding receptors. Contrarily, miRNAs enriched in Lean EVs target primarily EphrinA-EPHA and the Rho family of GTPases.
Conclusions
MetS alters the miRNA content of EVs derived from porcine adipose tissue MSCs. These alterations could impair the efficacy of autologous MSCs and limit its therapeutic use in subjects with MetS. Our findings may assist in developing adequate regenerative strategies to preserve the reparative potency of MSCs in individuals with MetS.