High aminopeptidase N/CD13 levels characterize human amniotic mesenchymal stem cells and drive their increased adipogenic potential in obese women

Stem Cells Dev. 2013 Aug 15;22(16):2287-97. doi: 10.1089/scd.2012.0499. Epub 2013 Apr 23.

Abstract

Maternal obesity is associated to increased fetal risk of obesity and other metabolic diseases. Human amniotic mesenchymal stem cells (hA-MSCs) have not been characterized in obese women. The aim of this study was to isolate and compare hA-MSC immunophenotypes from obese (Ob-) and normal weight control (Co-) women, to identify alterations possibly predisposing the fetus to obesity. We enrolled 16 Ob- and 7 Co-women at delivery (mean/SEM prepregnancy body mass index: 40.3/1.8 and 22.4/1.0 kg/m2, respectively), and 32 not pregnant women. hA-MSCs were phenotyped by flow cytometry; several maternal and newborn clinical and biochemical parameters were also measured. The expression of membrane antigen CD13 was higher on Ob-hA-MSCs than on Co-hA-MSCs (P = 0.005). Also, serum levels of CD13 at delivery were higher in Ob- versus Co-pregnant women and correlated with CD13 antigen expression on Ob-hA-MSCs (r2 = 0.84, P < 0.0001). Adipogenesis induction experiments revealed that Ob-hA-MSCs had a higher adipogenic potential than Co-hA-MSCs as witnessed by higher peroxisome proliferator-activated receptor gamma and aP2 mRNA levels (P = 0.05 and P = 0.05, respectively), at postinduction day 14 associated with increased CD13 mRNA levels from baseline to day 4 postinduction (P < 0.05). Adipogenesis was similar in the two sets of hA-MSCs after CD13 silencing, whereas it was increased in Co-hA-MSCs after CD13 overexpression. CD13 expression was high also in Ob-h-MSCs from umbilical cords or visceral adipose tissue of not pregnant women. In conclusion, antigen CD13, by influencing the adipogenic potential of hA-MSCs, could be an in utero risk factor for obesity. Our data strengthen the hypothesis that high levels of serum and MSC CD13 are obesity markers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis / genetics*
  • Adult
  • Amnion / enzymology*
  • Amnion / growth & development
  • Amnion / pathology
  • Body Mass Index
  • CD13 Antigens / antagonists & inhibitors
  • CD13 Antigens / genetics
  • CD13 Antigens / metabolism*
  • Case-Control Studies
  • Female
  • Gene Expression
  • Humans
  • Immunophenotyping
  • Infant, Newborn
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / enzymology*
  • Obesity / enzymology
  • Obesity / genetics*
  • Obesity / pathology
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Pregnancy
  • RNA, Messenger / antagonists & inhibitors
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Risk Factors

Substances

  • PPAR gamma
  • RNA, Messenger
  • RNA, Small Interfering
  • CD13 Antigens