title: High aminopeptidase N/CD13 levels characterize human amniotic mesenchymal stem cells and drive their increased adipogenic potential in obese women.
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.
authors.affiliation: CEINGE-Biotecnologie Avanzate S.C.a R.L., Naples, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Iaffaldano
authors.forename: Carmela
authors.initials: C
authors.lastname: Nardelli
authors.forename: Maddalena
authors.initials: M
authors.lastname: Raia
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Mariotti
authors.forename: Maddalena
authors.initials: M
authors.lastname: Ferrigno
authors.forename: Filomena
authors.initials: F
authors.lastname: Quaglia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Labruna
authors.forename: Valentina
authors.initials: V
authors.lastname: Capobianco
authors.forename: Angela
authors.initials: A
authors.lastname: Capone
authors.forename: Giuseppe Maria
authors.initials: GM
authors.lastname: Maruotti
authors.forename: Lucio
authors.initials: L
authors.lastname: Pastore
authors.forename: Rosa
authors.initials: R
authors.lastname: Di Noto
authors.forename: Pasquale
authors.initials: P
authors.lastname: Martinelli
authors.forename: Lucia
authors.initials: L
authors.lastname: Sacchetti
authors.forename: Luigi
authors.initials: L
authors.lastname: Del Vecchio
mesh_terms: D050156:Adipogenesis / Q000235:genetics*; D000328:Adult; D000650:Amnion / Q000201:enzymology* / Q000254:growth & development / Q000473:pathology; D015992:Body Mass Index; D018826:CD13 Antigens / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D007231:Infant, Newborn; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000201:enzymology*; D009765:Obesity / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors
chemical_list: D047495:PPAR gamma; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018826:CD13 Antigens