Proinflammatory interleukins' production by adipose tissue‐derived mesenchymal stromal cells: the impact of cell culture conditions and cell‐to‐cell interaction

Abstract

The impact of culture conditions and interaction with activated peripheral blood mononuclear cells on the interleukin (IL) gene expression profile and proinflammatory IL-6 and IL-8 production by adipose-derived stromal cells (ASCs) was investigated. A microarray analysis revealed a wide range of IL genes either under standard (20%) or hypoxic (5%) O2 concentrations, some highly up-regulated at hypoxia. IL-6 and IL-8 production was inversely dependent on cell culture density. In early (first-third) passages, IL-6 and IL-8 concentration was higher at 20% O2 and in late (8th-12th) passages under 5% O2. Interaction between ASCs and mononuclear cells in indirect setting was accompanied with a significant decrease of IL-6 and did not result in the elevation of IL-8 concentration. Thereby, the production of proinflammatory interleukins (IL-6 and IL-8) may be affected by the ASC intrinsic features (density in culture, and duration of expansion), as well as by microenvironmental factors, such as hypoxia and the presence of blood-borne cells. These data are important for elucidating ASC paracrine activity regulation in vitro. They would also be on demand for optimisation of the cell therapy protocols, based on the application of ASC biologically active substances. SIGNIFICANCE PARAGRAPH: Ex vivo expansion is widely used for increasing the number of adipose-derived stromal cells (ASCs) and improving of their quality. The present study was designed to elucidate the particular factors influencing the interleukin production in ASCs. The presented data specified the parameters (i.e. cell density, duration of cultivation, hypoxia, etc.) that should be taken in mind when ASCs are intended to be used in protocols implying their paracrine activity. These data would be of considerable interest for researchers and clinicians working in the biomedical science.

Preconditioning of Human Mesenchymal Stem Cells to Enhance Their Regulation of the Immune Response

“…Hypoxia-Treated MSCs and Adaptive Immunity. For the preconditioning of MSCs, hypoxic pretreatment enhances the immunomodulatory effect of MSCs by improving the secretion of cytokines and soluble factors related to immunosuppression [50][51][52]. For example, it has been reported that hypoxia modulates the cytokine profile of human gingivaderived MSCs (G-MSCs), by stimulating the production of anti-inflammatory cytokines, such as IL-10, and shifting the cytokine profile towards the anti-inflammatory mediators.…”

The Impact of Cell-Expansion and Inflammation on The Immune-Biology of Human Adipose Tissue-Derived Mesenchymal Stromal Cells

“…In vitro expansion is of relevance to allow suitable amount of AT-MSCs for transplantation. It is clear from the literature that this in vitro expansion of MSCs can lead to distinct changes in MSCs phenotype [33], so defining expansion and environmental conditions, which are important for the biology of the cells, have to be considered when these cells are intended to be used for clinical scale-up [36].…”