Abstract
BackgroundIn the field of diabetes research, many studies on cell therapy have been conducted using mesenchymal stem cells. This research was intended to shed light on the influence of canine adipose-tissue-derived mesenchymal stem cell conditioned medium (cAT-MSC CM) on in vitro insulin resistance models that were induced in differentiated 3T3-L1 adipocytes and the possible mechanisms involved in the phenomenon.ResultsGene expression levels of insulin receptor substrate-1 (IRS-1) and glucose transporter type 4 (GLUT4) were used as indicators of insulin resistance. Relative protein expression levels of IRS-1 and GLUT4 were augmented in the cAT-MSC CM treatment group compared to insulin resistance models, indicating beneficial effects of cAT-MSC to DM, probably by actions of secreting factors. With reference to previous studies on fibroblast growth factor-1 (FGF1), we proposed FGF1 as a key contributing factor to the mechanism of action. We added anti-FGF1 neutralizing antibody to the CM-treated insulin resistance models. As a result, significantly diminished protein levels of IRS-1 and GLUT4 were observed, supporting our assumption. Similar results were observed in glucose uptake assay.ConclusionsAccordingly, this study advocated the potential of FGF-1 from cAT-MSC CM as an alternative insulin sensitizer and discovered a signalling factor associated with the paracrine effects of cAT-MSC.
Highlights
In the field of diabetes research, many studies on cell therapy have been conducted using mesenchymal stem cells
Characterization of cAT-Mesenchymal stem cells (MSCs) Cells obtained from canine adipose tissue were characterized by their ability to express stem cell markers and to differentiate toward adipogenic, osteogenic, and chondrogenic lineages when cultured in media containing lineage-specific factors
The anti-fibroblast growth factor-1 (FGF1) antibody group represented diminished expression levels of insulin resistance markers in Conclusions We identified that the induced insulin resistance in 3T3-L1 cells was ameliorated in the presence of cAT-MSC conditioned medium (CM) by measuring mRNA and protein expression levels of insulin receptor substrate-1 (IRS-1) and glucose transporter type 4 (GLUT4)
Summary
In the field of diabetes research, many studies on cell therapy have been conducted using mesenchymal stem cells. This research was intended to shed light on the influence of canine adipose-tissue-derived mesenchymal stem cell conditioned medium (cAT-MSC CM) on in vitro insulin resistance models that were induced in differentiated 3T3-L1 adipocytes and the possible mechanisms involved in the phenomenon. Several reports advocate that concurrent diseases such as obesity and inflammatory diseases are associated with insulin resistance in human DM patients [1,2,3,4]. A. Mesenchymal stem cells (MSCs) are multipotent stromal cells that have immunomodulatory and regenerative effects. Mesenchymal stem cells (MSCs) are multipotent stromal cells that have immunomodulatory and regenerative effects Because they are relatively free from ethical issues, their therapeutic uses for various diseases including DM have been studied globally.
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