Journal
STEM CELLS
Volume 34, Issue 10, Pages 2559-2573Publisher
WILEY
DOI: 10.1002/stem.2429
Keywords
Human adipose stem cells; Obesity; Diabetes; Invasion; Migration; Phagocytosis; Inflammasome; Immunosuppression; Macrophages; Inflammation
Categories
Funding
- Spanish Ministry of Economy and Competitiveness [PI14/00228, SAF2012-36186, SAF2015-65019-R, PI15/00143]
- European Regional Development Fund (ERDF)
- Ramon y Cajal program from the Ministerio de Educacion y Ciencia [RYC2013-13186]
- Miguel Servet tenure track program from the Fondo de Investigacion Sanitaria (FIS) [CP10/00438]
Ask authors/readers for more resources
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-1 secretion, than lean-derived ASCs. Treatment of lean hASCs with interleukin (IL)-1 mimicked the dysfunctional immune behavior of obese and T2D hASCs. Conversely, combined treatment with IL1RA and TGF-1 reverted the phenotype of obese- and T2D-ASCs. These data indicate that the donor metabolic phenotype compromises the immunomodulatory properties of ASCs. These results are relevant not only for understanding the physiology of ASCs in terms of cell-based therapies but also for their role as key regulators of the immune response. Stem Cells2016;34:2559-2573
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available