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/m 2 , 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 (r 2 = 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.

Mesenchymal Stem Cells From Infants Born to Obese Mothers Exhibit Greater Potential for Adipogenesis: The Healthy Start BabyBUMP Project

“…With regard to maternal obesity and fetal programming events, our results are also consistent with greater adipogenesis in human placental amnion–derived MSCs, where CD13/APN content is elevated and necessary for greater adipogenesis in MSCs from offspring of obese mothers and CD13/APN overexpression is sufficient for inducing greater adipogenesis in MSCs from offspring of NW mothers ( 26 ). While CD13/APN is considered a common MSC marker that has been linked to cancer and T-cell proliferation via ERK/mitogen-activated protein kinase signaling ( 37 ) and inflammatory and angiogenic mechanisms in vitro ( 38 ), very few groups have investigated obesity-related differences in CD13/APN content or function.…”

“…We measured CD13/APN, a potential novel marker of adipogenic potential ( 26 ), in undifferentiated cells using flow cytometry. The percent of cells gated at each step was similar for all subjects, indicating no overt differences in cell size, density, or viability ( Fig.…”

Proteome analysis of human amniotic mesenchymal stem cells (hA-MSCs) reveals impaired antioxidant ability, cytoskeleton and metabolic functionality in maternal obesity

“…We recently reported that the adipogenic potential of hA-MSCs isolated from obese women (Ob-hA-MSCs) was higher than that of hA-MSCs from lean control women (Co-hA-MSCs) 8 . In detail, we demonstrated that high levels of CD13/aminopeptidase N on the Ob-hA-MSC surface, measured by immunophenotyping, resulted in enhanced adipogenesis of these cells, which, in turn, could be related to the pathogenesis of obesity 8 .…”

Filamin B and CD13 are components of senescent secretomes that may be involved in primary (stress induced) and paracrine senescence of mesenchymal stromal cells

“…proliferation, differentiation, proliferation, apoptosis, invasion, secretion, motility and angiogenesis) (21,22). An intriguing study conducted by Iaffaldano et al suggested that CD13 could contribute to obesity programming in the fetus and that high maternal serum CD13 represent an obesity risk marker (23). Interestingly, it has been widely demonstrated that obesity is associated with an increase of senescent cells since it can contribute to create an environment that accelerates senescence within the tissues of the organism (24,25).…”