Obesity Determines the Immunophenotypic Profile and Functional Characteristics of Human Mesenchymal Stem Cells From Adipose Tissue

Abstract

Adipose tissue is a major source of mesenchymal stem cells (MSCs), which possess a variety of properties that make them ideal candidates for regenerative and immunomodulatory therapies. Here, we compared the immunophenotypic profile of human adipose-derived stem cells (hASCs) from lean and obese individuals, and explored its relationship with the apparent altered plasticity of hASCs. We also hypothesized that persistent hypoxia treatment of cultured hASCs may be necessary but not sufficient to drive significant changes in mature adipocytes. hASCs were obtained from subcutaneous adipose tissue of healthy, adult, female donors undergoing abdominal plastic surgery: lean (n = 8; body mass index [BMI]: 23 6 1 kg/m 2 ) and obese (n = 8; BMI: 35 6 5 kg/m 2 ). Cell surface marker expression, proliferation and migration capacity, and adipogenic differentiation potential of cultured hASCs at two different oxygen conditions were studied. Compared with lean-derived hASCs, obese-derived hASCs demonstrated increased proliferation and migration capacity but decreased lipid droplet accumulation, correlating with a higher expression of human leukocyte antigen (HLA)-II and cluster of differentiation (CD) 106 and lower expression of CD29. Of interest, adipogenic differentiation modified CD106, CD49b, HLA-ABC surface protein expression, which was dependent on the donor's BMI. Additionally, low oxygen tension increased proliferation and migration of lean but not obese hASCs, which correlated with an altered CD36 and CD49b immunophenotypic profile. In summary, the differences observed in proliferation, migration, and differentiation capacity in obese hASCs occurred in parallel with changes in cell surface markers, both under basal conditions and during differentiation. Therefore, obesity is an important determinant of stem cell function independent of oxygen tension. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:464-475 SIGNIFICANCEThe obesity-related hypoxic environment may have latent effects on human adipose tissue-derived mesenchymal stem cells (hASCs) with potential consequences in mature cells. This study explores the immunophenotypic profile of hASCs obtained from lean and obese individuals and its potential relationship with the altered plasticity of hASCs observed in obesity. In this context, an altered pattern of cell surface marker expression in obese-derived hASCs in both undifferentiated and differentiated stages is demonstrated. Differences in proliferation, migration, and differentiation capacity of hASCs from obese adipose tissue correlated with alterations in cell surface expression. Remarkably, altered plasticity observed in obese-derived hASCs was maintained in the absence of hypoxia, suggesting that these cells might be obesity conditioned.

Insight into the development of obesity: functional alterations of adipose‐derived mesenchymal stem cells

“…However, it is also reported that ASCs isolated from the subcutaneous abdominal adipose tissue of obese patients demonstrated an increased ability in invasion associated with the expression of calpain‐4, calpastatin and MMP‐15 . The immunophenotypic profile and the migration pattern were compared between human lean and obese ASCs . Relative to lean ASCs, obese ASCs showed an increased basal migration capacity, correlating with a higher expression of human leukocyte antigen (HLA)‐II .…”

“…The immunophenotypic profile and the migration pattern were compared between human lean and obese ASCs . Relative to lean ASCs, obese ASCs showed an increased basal migration capacity, correlating with a higher expression of human leukocyte antigen (HLA)‐II . Yet, low oxygen tension increased migration of lean but not obese ASCs, which correlated with an altered CD36 and CD49b immunophenotypic profile .…”

“…Relative to lean ASCs, obese ASCs showed an increased basal migration capacity, correlating with a higher expression of human leukocyte antigen (HLA)‐II . Yet, low oxygen tension increased migration of lean but not obese ASCs, which correlated with an altered CD36 and CD49b immunophenotypic profile . Interestingly, a recent study reports that obese patients with prostate cancer have an increased epithelial expression of chemokine C‐X‐C motif ligand 1 (CXCL1) and cells with ASC phenotype are mobilized and infiltrate tumours in obese patients .…”

Adipose stem cells from obese patients show specific differences in the metabolic regulators vitamin D and Gas5

“…AT also serves as a novel source of adult stem cells, termed adipose stem cells (ASCs), which have great potential for therapeutic applications [5]. However, we and others have shown that the environmental niche in which ASCs reside has a profound impact on their functional properties [6], [7], [8].…”

Unhealthy Stem Cells: When Health Conditions Upset Stem Cell Properties

“…Subcutaneous adipose tissue from obese patients has a diminished reservoir of functionally active stem cells [85]. Moreover, metabolism and maturation of APCs are arrested in an obese environment [17], and their ability to migrate or invade a tissue is impaired [86, 87]. Mechanistically, obesity causes a short circuit in the stemness gene network [88], promoting an imbalance in metabolism and a reduction in stemness properties [89].…”