Altered metabolic and stemness capacity of adipose tissue-derived stem cells from obese mouse and human

PLoS One. 2015 Apr 13;10(4):e0123397. doi: 10.1371/journal.pone.0123397. eCollection 2015.

Abstract

Adipose stem cells (ASCs) are an appealing source of cells for therapeutic intervention; however, the environment from which ASCs are isolated may impact their usefulness. Using a range of functional assays, we have evaluated whether ASCs isolated from an obese environment are comparable to cells from non-obese adipose tissue. Results showed that ASCs isolated from obese tissue have a reduced proliferative ability and a loss of viability together with changes in telomerase activity and DNA telomere length, suggesting a decreased self-renewal capacity. Metabolic analysis demonstrated that mitochondrial content and function was impaired in obese-derived ASCs resulting in changes in favored oxidative substrates. These findings highlight the impact of obesity on adult stem properties. Hence, caution should be exercised when considering the source of ASCs for cellular therapies since their therapeutic potential may be impaired.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology*
  • Adipose Tissue / pathology*
  • Adult
  • Animals
  • Base Sequence
  • Body Mass Index
  • Cell Proliferation
  • Cell Survival
  • DNA / analysis
  • Fatty Acids / chemistry
  • Female
  • Humans
  • Lactic Acid / chemistry
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Mitochondria / metabolism
  • Molecular Sequence Data
  • Obesity / metabolism*
  • Reactive Oxygen Species / metabolism
  • Stem Cells / cytology*
  • Telomere / ultrastructure

Substances

  • Fatty Acids
  • Reactive Oxygen Species
  • Lactic Acid
  • DNA

Grants and funding

This study was supported by grants from the Spanish Ministry of Science and Innovation (SAF 2010-15239) to BGG. BGG also acknowledges support from the “Ramon y Cajal” tenure track programme from the Spanish Ministry of Science and Innovation (RYC2009-04669). The CNIC is supported by the Spanish Ministry of Science and Innovation and the Pro-CNIC Foundation. LMP and AB are supported by FPI fellowships from the Spanish Ministry. AM is supported by a fellowship from the Spanish Ministry of Economy and Competitiveness (MINECO, CTQ2011-23562). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.