Abstract
We investigated whether maternal metabolic environment affects mesenchymal stromal/stem cells (MSCs) from umbilical cord’s Wharton’s Jelly (WJ) on a molecular level, and potentially render them unsuitable for clinical use in multiple recipients. In this pilot study on umbilical cords post partum from healthy non-obese (BMI = 19–25; n = 7) and obese (BMI ≥ 30; n = 7) donors undergoing elective Cesarean section, we found that WJ MSC from obese donors showed slower population doubling and a stronger immunosuppressive activity. Genome-wide DNA methylation of triple positive (CD73+CD90+CD105+) WJ MSCs found 67 genes with at least one CpG site where the methylation difference was ≥0.2 in four or more obese donors. Only one gene, PNPLA7, demonstrated significant difference on methylome, transcriptome and protein level. Although the number of analysed donors is limited, our data suggest that the altered metabolic environment related to excessive body weight might bear consequences on the WJ MSCs.
Highlights
We investigated whether maternal metabolic environment affects mesenchymal stromal/stem cells (MSCs) from umbilical cord’s Wharton’s Jelly (WJ) on a molecular level, and potentially render them unsuitable for clinical use in multiple recipients
To evaluate whether the altered metabolic environment related to excessive body weight might bear consequences for the use of umbilical cord WJ MSCs in cellular therapy, we compared their growth, differentiation propensity into adipo, chondroand osteogenic lineages, immunomodulatory effect, genome-wide DNA methylation and transcriptome analyses in early passages of WJ MSCs isolated from healthy non-obese and obese donors (Figure S1)
Since MSC have the ability of exerting potent immunosuppressive and immunoregulatory effects[21,22,23], we investigated whether the altered metabolic environment of the obese pregnancies affects WJ MSC immunomodulatory properties
Summary
Growth and phenotypic profile of WJ MSCs from obese and non-obese donors show significant differences in population doubling (PD) time and CD56 expression. The majority of the cells in both groups were positive for all standard MSC markers (CD29, CD56, CD44, CD73, CD90 and CD105), Mann-Whitney testing of the expression profiles demonstrated significant difference between non-obese and obese donors in expression level of CD56, which showed significantly lower expression levels in cells from obese than non-obese donors (p = 0.025) (Fig. 1D). Per Wilcoxon signed rank test, the expression of chondrogenic marker COLL11A1, as assessed by qPCR, showed significant increase in WJ MSC from both non-obese and obese donors upon differentiation (***p ≤ 0.001), indicating chondrogenesis (right). Among the remaining 16 genes with significantly different methylation of CpG sites between two groups, only one, Patatin-like Phospholipase Domain containing Protein A 7(PNPLA7), had significantly different mRNA expression levels between non-obese and obese groups (Fig. 5I). Actin, used as an essay control, showed no significant difference between the obese and non-obese group
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