Individual Variabilities in Adipose Stem Cell Proliferation, Gene Expression and Responses to Lipopolysaccharide Stimulation

Int J Mol Sci. 2022 Oct 19;23(20):12534. doi: 10.3390/ijms232012534.

Abstract

Adipose stem cells (ASCs) are reported to play a role in normal physiology as well as in inflammation and disease. The objective of this work was to elucidate inter-individual differences in growth, gene expression and response to inflammatory stimuli in ASCs from different donors. Human ASC1 (male donor) and ASC2 (female donor) were purchased from Lonza (Walkersville, MD). Cell proliferation was determined by the sulforhodamine B assay. After time-dependent treatment of ASCs with or without bacterial lipopolysaccharide (LPS), marker gene mRNAs for proliferation, steroid hormones, and xenobiotic and immune pathways were determined using RT-PCR, and secreted cytokine levels in media were measured using the Bio-Plex cytokine assay kit. ASCs from both donors expressed androgen receptors but not estrogen receptors. ASC2 had a 2-fold higher proliferation rate and a 6-fold higher level of proliferation marker Ki67 mRNA than ASC1. ASC2 exhibited significantly greater fold induction of TNF-α and CCL2 by LPS compared to ASC1. TNF-α and GM-CSF protein levels were also significantly higher in the LPS-induced ASC2 media, but IL-6 secretion was higher in the LPS-induced ASC1 media. Our findings suggest that inter-individual variability and/or possible sex differences exist in ASCs, which may serve as a key determinant to inflammatory responses of ASCs.

Keywords: LPS; adipose stem cell; individual differences; inflammation; sex.

MeSH terms

  • Adipose Tissue / metabolism
  • Cell Proliferation
  • Cytokines / genetics
  • Cytokines / metabolism
  • Female
  • Gene Expression
  • Granulocyte-Macrophage Colony-Stimulating Factor* / metabolism
  • Hormones / metabolism
  • Humans
  • Interleukin-6 / metabolism
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism
  • Lipopolysaccharides* / metabolism
  • Lipopolysaccharides* / pharmacology
  • Male
  • RNA, Messenger / metabolism
  • Receptors, Androgen / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Xenobiotics / metabolism

Substances

  • Lipopolysaccharides
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Ki-67 Antigen
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Receptors, Androgen
  • Xenobiotics
  • RNA, Messenger
  • Cytokines
  • Hormones