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* = Presenting author

P034 Immunoregulatory properties of human adipose–derived stem cells in inflammatory diseases: differences between Crohn´s disease and obesity

C. Serena*1, 2, N. Keiran2, M. Millan2, M. Ejarque1, 2, R. Fradera3, E. Espin4, K. Roche1, 2, J. Vendrell1, 2, S. Fernandez-Veledo1, 2

1Health Institute Pere Virgili, Research Unit, Tarragona, Spain, 2Hospital Joan XXIII, Tarragona, Spain, 3Hospital St. Pau i Sta Tecla, Tarragona, Spain, 4Hospital Vall d’Hebron, Barcelona, Spain

Background

Inflammation and dysbiosis are common soils in several highly prevalent diseases, such as Crohn’s disease (CD), obesity, and type 2 diabetes (T2D). Visceral fat depot plays a decisive role in the inflammatory environmental observed in these pathologies. Specifically, in CD subjects there is frequently a body weight-independent characteristic hyperplasia of the mesenteric fat tissue, which is called creeping fat (CF). However, CD patients show an aggressive local inflammatory response, whereas obese and T2D patients develop a subtle chronic inflammatory status. The main objective of this study was to identify key factors involved in triggering the immune innate response of adipose tissue (AT). Specifically, we focus on the potential role that human adipose–derived stem cells (hASCs) play in local and systemic inflammation in the setting of CD and obesity.

Methods

We isolated hASCs from subcutaneous (SAT) and visceral adipose tissue (VAT) (visceral origin: CF in CD subjects and mesenteric in obese subjects) of a well-characterised cohort including 4 groups: inactive CD (in remission), active CD, obese, and obese subjects with associated metabolic morbidities. Each group was composed of least by 3 donors. hASCs were immunophenotyped by flow cytometry using the fluorescein isothiocyanate–conjugated antihuman mouse antibodies (eg, anti-CD34, anti-CD45, anti-CD73, and anti-CD90). Gene expression profile, migration, invasion, and proliferation, as well as phagocytic capacity were analysed in hASCs obtained from different donors.

Results

hASCs obtained from CD subjects has shown a significantly greater proliferative, migratory, and more interestingly invasive and phagocytic capacity than those derived from obese subjects, regardless of the presence of other metabolic disturbances (see Figure 1). This distinctive difference in phenotype between CD versus obese hASCs was observed in both active and inactive CD donors. Accordingly, AT inflammation markers (IL-6, TNFα, IL-1β, and MCP-1) indicated that both active and inactive CD subjects present a higher pro-inflammatory environment compared with obese subjects. Remarkably, we demonstrate that CD produces a detrimental effect on not only mesenteric adipose tissue-resident stem cells but also the subcutaneous fat depots.

Figure 1. Human adipose derived stem sells (hASCs) isolated from Crohn’s disease (CD) subjects exhibit a phagocytic cell functional response with a higher migration and invasion capacity that those derived from obese (Ob) subjects. A. Phagocytic activity. B. Migration activity C. Invasion markers. * P<0.05 vs obese hASCs. $ P<0.01 as indicated in the figure. SAT: VAT. T2D, type 2 diabetic. MMP2 and MMP9, matrix Metalloproteinase-2 and 9, respectively.

Conclusion

hASCs may have different immuno-modulatory capacities depending on the inflammatory event. Further work will be required to define whether hASCs response is protective or contributes to the associated metabolic derangements of these inflammatory diseases.