Format

Send to

Choose Destination
Exp Biol Med (Maywood). 2014 Oct;239(10):1340-51. doi: 10.1177/1535370214539225. Epub 2014 Jun 20.

Distinct adipogenic differentiation phenotypes of human umbilical cord mesenchymal cells dependent on adipogenic conditions.

Author information

1
Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA.
2
Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA.
3
Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA ShankarKartik@uams.edu.

Abstract

The umbilical cord (UC) matrix is a source of multipotent mesenchymal stem cells (MSCs) that have adipogenic potential and thus can be a model to study adipogenesis. However, existing variability in adipocytic differentiation outcomes may be due to discrepancies in methods utilized for adipogenic differentiation. Additionally, functional characterization of UCMSCs as adipocytes has not been described. We tested the potential of three well-established adipogenic cocktails containing IBMX, dexamethasone, and insulin (MDI) plus indomethacin (MDI-I) or rosiglitazone (MDI-R) to stimulate adipocyte differentiation in UCMSCs. MDI, MDI-I, and MDI-R treatment significantly increased peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT-enhancer binding protein alpha (C/EBPα) mRNA and induced lipid droplet formation. However, MDI-I had the greatest impact on mRNA expression of PPARγ, C/EBPα, FABP4, GPD1, PLIN1, PLIN2, and ADIPOQ and lipid accumulation, whereas MDI showed the least. Interestingly, there were no treatment group differences in the amount of PPARγ protein. However, MDI-I treated cells had significantly more C/EBPα protein compared to MDI or MDI-R, suggesting that indomethacin-dependent increased C/EBPα may contribute to the adipogenesis-inducing potency of MDI-I. Additionally, bone morphogenetic protein 4 (BMP4) treatment of UCMSCs did not enhance responsiveness to MDI-induced differentiation. Finally to characterize adipocyte function, differentiated UCMSCs were stimulated with insulin and downstream signaling was assessed. Differentiated UCMSCs were responsive to insulin at two weeks but showed decreased sensitivity by five weeks following differentiation, suggesting that long-term differentiation may induce insulin resistance. Together, these data indicate that UCMSCs undergo adipogenesis when differentiated in MDI, MDI-I, and MDI-R, however the presence of indomethacin greatly enhances their adipogenic potential beyond that of rosiglitazone. Furthermore, our results suggest that insulin signaling pathways of differentiated UCMSCs are functionally similar to adipocytes.

KEYWORDS:

Adipogenesis; insulin signaling; mesenchymal stem cells; peroxisome proliferator-activated receptor gamma; umbilical cord

PMID:
24951473
PMCID:
PMC4238288
DOI:
10.1177/1535370214539225
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center