Individual variabilities in adipose stem cell proliferation, gene expression and responses to lipopolysaccharide stimulation

Authors: YASMIN, RUMANA - Food And Drug Administration(FDA); Pham, Quynhchi; Fukagawa, Naomi; Wang, Thomas - Tom

Submitted to: International Journal of Molecular Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/18/2022
Publication Date: 10/19/2022
Citation: Yasmin, R., Pham, Q., Fukagawa, N.K., Wang, T.T. 2022. Individual variabilities in adipose stem cell proliferation, gene expression and responses to lipopolysaccharide stimulation. International Journal of Molecular Sciences. 23:12534. https://doi.org/10.3390/ijms232012534.
DOI: https://doi.org/10.3390/ijms232012534

Interpretive Summary: To realized the goals of precision nutrition/personalized nutrition, detail understanding of individual difference at the cellular and molecular levels are necessary. Adipose stem cells (ASC) are reported to play a role in normal physiology, inflammation as well as diseases. The objective of this work was to elucidate inter-individual differences in growth, gene expression and response to inflammatory stimuli in ASC from different donors. Human ASC1 (male donor) and ASC2 (female donor) were purchased from Lonza (Walkersville, MD). Cell proliferation was determined by the sulforhodamine B assay. After time-dependent treatment of ASC with or without bacterial lipopolysaccharide (LPS), marker genes mRNA for proliferation, steroid hormones, xenobiotic and immune pathways were determined using RT-PCR and secreted cytokine levels in media were measured using the Bio-Plex cytokine assay kit. Results: ASCs expressed the androgen receptor but not the estrogen receptors. ASC2 had a 2-fold higher proliferation rate and 6-fold higher proliferation marker Ki67 mRNA than ASC1. ASC2 exhibited a significantly greater fold induction of TNF-a and CCL2 by LPS as compared to ASC1. TNF-a, GM-CSF protein were also significantly higher in the LPS-induced ASC2 media, but IL-6 secretion was higher in the LPS-induced ASC1 media.  Our findings suggest that inter-individual variability and/or possible sex differences exist in ASC which may serve as a key determinant to inflammatory responses of ASC. This study provide novel information on individual differences in adipose stem cell physiological properties and their respond to inflammatory stimuli. The information will benefit basic and translational scientist working on precision nutrition/personalized nutrition .

Technical Abstract: Adipose stem cells (ASC) are reported to play a role in normal physiology, inflammation as well as diseases. The objective of this work was to elucidate inter-individual differences in growth, gene expression and response to inflammatory stimuli in ASC from different donors. Methods: Human ASC1 (male donor) and ASC2 (female donor) were purchased from Lonza (Walkersville, MD). Cell proliferation was determined by the sulforhodamine B assay. After time-dependent treatment of ASC with or without bacterial lipopolysaccharide (LPS), marker genes mRNA for proliferation, steroid hormones, xenobiotic and immune pathways were determined using RT-PCR and secreted cytokine levels in media were measured using the Bio-Plex cytokine assay kit. Results: ASCs expressed the androgen receptor but not the estrogen receptors. ASC2 had a 2-fold higher proliferation rate and 6-fold higher proliferation marker Ki67 mRNA than ASC1. ASC2 exhibited a significantly greater fold induction of TNF-a and CCL2 by LPS as compared to ASC1. TNF-a, GM-CSF protein were also significantly higher in the LPS-induced ASC2 media, but IL-6 secretion was higher in the LPS-induced ASC1 media.  Conclusions: Our findings suggest that inter-individual variability and/or possible sex differences exist in ASC which may serve as a key determinant to inflammatory responses of ASC.