1180-P: Impact of Diabetes Exposure In Utero on Mesenchymal Stem Cell Phenotype and Metabolic Function

Abstract

Fetal programming events at the level of the MSC not only direct development of fetal tissues in utero but may also impact these tissues throughout the life span. Exposure to diabetes (DM) in utero appears to affect early programming of MSC; thus, we hypothesized that the phenotype and metabolic characteristics of MSC would be altered by exposure to the diabetic milieu. MSC were isolated from umbilical cord Wharton's Jelly within 24 hours of delivery and confirmed by the presence of CD105 and CD90 and absence of CD34 and CD45. To assess the adipogenic capacity of MSC, they were stained with CD13 or isotype-control antibody. DM-exposed MSC revealed a 14% increase in CD13 abundance (p=0.12) compared to control MSC, indicating a higher propensity for adipocyte differentiation. Changes in energy expenditure were assessed using the Seahorse XF Cell Mito Stress Kit at passage 4-8. Maximal respiration and spare respiratory capacity were reduced by 66% (p=0.08) and 51% (p=0.08), respectively, in the DM MSC (N=3) compared to the control MSC (N=4) (Figure 1). Basal respiration and ATP production did not differ. In this pilot study, reductions in maximal respiration and spare capacity suggest that DM exposure alters the MSC's ability to meet metabolic demands under stress. Further work is needed to understand the exact mechanisms by which exposure to DM in utero alters MSC metabolism and phenotype. Disclosure W.Lee: None. D.Redling: None. O.Brooks: None. A.M.Teague: None. S.Jiang: None. J.B.Tryggestad: None. Funding National Institutes of Health (1K23DK106533, R03DK125626, P30GM122744)