Abstract
Adipose-derived stromal/stem cells (ASCs) are adult stem cells that have the potential to differentiate into mesenchymal lineage cells. The abundance of ASCs in adipose tissue and easy accessibility with relatively little donor site morbidity make them attractive candidate cells for tissue engineering and regenerative medicine. However, the underlying inflammatory process that occurs during ASC differentiation into adipocytes and osteoblast has not been extensively investigated. ASCs cultured in osteogenic and adipogenic differentiation medium were characterized by oil red o staining and alizarin red staining, respectively. ASCs undergoing osteogenic and adipogenic differentiation were isolated on days 7, 14, and 21 and assessed by qRT-PCR for the expression of pro- and anti-inflammatory cytokines. ASCs undergoing osteogenic differentiation expressed a distinct panel of cytokines that differed from the cytokine profile of ASCs undergoing adipogenic differentiation at each of the time points analyzed. Mapping the cytokine expression profile during ASC differentiation will provide insight into the role of inflammation in this process and identify potential targets that may aid in enhancing osteogenic or adipogenic differentiation for the purposes of tissue engineering and regenerative medicine.
Highlights
Adipose-derived stromal/stem cells (ASCs) are adult stem cells with multipotential differentiation capacity
Induction of CCAAT-enhancer-binding proteins (C/EBPβ, CCAAT-enhancer-binding proteins delta CCL2 (C/EBPδ)) and peroxisome proliferator-activated receptor delta (PPARδ) expression occurs during early adipogenic differentiation, while fatty acid binding protein 4 (FABP4), CCAAT-enhancer-binding proteins alpha C/EBPβ (C/EBPα), lipoprotein lipase (LPL), leptin, and glucose transporter 4 (GLUT4)
ASCs were isolated from processed lipoaspirates harvested from subcutaneous adipose tissue and characterized based on differentiation potential, self-renewal capacity, and cell surface marker profile
Summary
Adipose-derived stromal/stem cells (ASCs) are adult stem cells with multipotential differentiation capacity. The osteogenic and adipogenic differentiation of ASCs has been shown to require the activation of key transcriptional factors that govern cell fate. RUNX2 has previously been shown to be a master regulator of osteoblast differentiation, as RUNX2 activates and regulates many osteogenic signaling pathways, including but not limited to transforming growth factor beta (TGF-β), bone morphogenetic protein (BMP), Wingless type Wnt, and Hedgehog [5, 6]. ASCs cultured in osteogenic differentiation medium have been shown to upregulate a key osteogenic factor dickkopf Wnt signaling pathway inhibitor 1 (DKK-1), as early as one day. Additional osteogenic transcriptional factors (connective tissue growth factor (CTGF), platelet-derived growth factor receptor beta (PDGFR-β), TGF-β, insulin-like growth factor binding protein 3 (IGFBP3), and tenascin C (TNC)) were induced after 7 days in osteogenic differentiation medium [7]. Induction of CCAAT-enhancer-binding proteins (C/EBPβ, C/EBPδ) and peroxisome proliferator-activated receptor delta (PPARδ) expression occurs during early adipogenic differentiation, while fatty acid binding protein 4 (FABP4), C/EBPα, lipoprotein lipase (LPL), leptin, and glucose transporter 4 (GLUT4)
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