Obesity and Type 2 Diabetes Alters the Immune Properties of Human Adipose Derived Stem Cells.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Adipose tissue-derived stem cells (ASCs) are proposed as an alternative stem cell source to bone marrow-derived cells for immune cell therapy. However, microenvironmental factors may impact the functionality of this population in human adipose tissue (AT). We hypothesized that the fat depot in addition to the donor phenotype controls the immunomodulatory capacity of ASCs. Focusing on obesity and type 2 diabetes (T2D) as metabolic disorders that might affect the immune response of ASCs, we compared the inflammatory response of ASCs from subcutaneous and visceral AT of age-matched donors (lean n = 4, body mass index [BMI] 21.98 ± 1.9; obese n = 4 BMI 33.1 ± 2.1 and T2D n = 4 BMI 35.3 ± 1.5). Obese and particularly T2D-derived ASCs showed increased expression of inflammatory markers, activation of NLRP3 inflammasome and higher migration, invasion and phagocytosis capacities than those derived from lean donors. Remarkably, ASCs derived from obese and T2D subjects exhibited a reduction in typical immunosuppressive activities attributed to stem cells. Accordingly, obese and T2D-ASCs were less effective in suppressing lymphocyte proliferation, activating the M2 macrophage phenotype, and in increasing TGF-β1 secretion, than lean-derived ASCs. Treatment of lean hASCs with interleukin (IL)-1β mimicked the dysfunctional immune behavior of obese and T2D hASCs. Conversely, combined treatmen

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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