Adipose-Derived Mesenchymal Stem Cells Isolated from Patients with Abdominal Aortic Aneurysm Exhibit Senescence Phenomena

Oxid Med Cell Longev. 2019 Nov 25:2019:1305049. doi: 10.1155/2019/1305049. eCollection 2019.

Abstract

Mesenchymal stem cells (MSCs) have shown beneficial effects in the treatment of abdominal aortic aneurysm (AAA). Nonetheless, the biological properties of adipose-derived MSCs (ASCs) from patients with AAA (AAA-ASCs) remain unclear. This study is aimed at investigating the properties of cell phenotype and function of AAA-ASCs compared with ASCs from age-matched healthy donors (H-ASCs). H-ASCs and AAA-ASCs were studied for cell phenotype, differentiation capacity, senescence, and mitochondrial and autophagic functions. Cellular senescence was examined by senescence-associated β-galactosidase (SA-β-gal) staining. Mitochondrial morphology was determined by MitoTracker staining. Despite the similar surface markers of AAA-ASCs and H-ASCs, AAA-ASCs exhibited altered multidifferentiation potential. Compared with H-ASCs, AAA-ASCs displayed enhanced senescence manifested by increased SA-β-gal activity and decreased proliferation and migration ability. Furthermore, AAA-ASCs showed increased mitochondrial fusion, reactive oxygen species (ROS) production, and decreased mitochondrial membrane potential. In addition, AAA-ASCs exhibited decreased autophagy level, upregulation of IL-6 and TNF-α secretion, and downregulation of IL-10 secretion compared with H-ASCs. Nonetheless, treatment of AAA-ASCs with rapamycin (an autophagy activator) dramatically reduced secretion of IL-6 and TNF-α and enhanced secretion of IL-10. In conclusion, our study showed that AAA-ASCs exhibit senescence phenomena and decreased cell function. Understanding the specific alterations in AAA-ASCs will help explore novel strategies to restore cell function for AAA treatment.

MeSH terms

  • Adipose Tissue / cytology
  • Aged
  • Aortic Aneurysm, Abdominal / metabolism
  • Aortic Aneurysm, Abdominal / pathology*
  • Autophagy
  • Case-Control Studies
  • Cell Movement
  • Cell Proliferation
  • Cellular Senescence*
  • DNA Damage
  • Female
  • Humans
  • Male
  • Membrane Potential, Mitochondrial
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Middle Aged
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Reactive Oxygen Species / metabolism

Substances

  • Microtubule-Associated Proteins
  • Reactive Oxygen Species