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

• Published in: Stem cells translational medicine 2016-04, Vol.5 (4), p.464-475
• Main Authors: Pachón-Peña, Gisela, Serena, Carolina, Ejarque, Miriam, Petriz, Jordi, Duran, Xevi, Oliva-Olivera, W., Simó, Rafael, Tinahones, Francisco J., Fernández-Veledo, Sonia, Vendrell, Joan
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipocytes - physiology; Adipogenesis - physiology; Adipogenic differentiation; Adipose tissue; Adipose Tissue - metabolism; Adipose Tissue - pathology; Adult; Body fat; Body mass index; Cell Differentiation; Cell Hypoxia; Cell surface; Cells, Cultured; Female; Flow Cytometry; Gene expression; Human mesenchymal stem cells; Humans; Hypoxia; Immunoglobulins; Immunophenotype; Immunophenotyping; Mesenchymal stem cells; Mesenchymal Stromal Cells - metabolism; Mesenchymal Stromal Cells - pathology; Mesenchymal Stromal Cells - physiology; Mesenchyme; Obesity; Obesity - metabolism; Obesity - pathology; Oxygen tension; Penicillin; Physiology; Plasticity; Stem cells; Studies; Surface markers; Surgery; Thinness - metabolism; Thinness - pathology; Tissue-Specific Progenitor and Stem Cells
• ISSN: 2157-6564; 2157-6580
• DOI: 10.5966/sctm.2015-0161

Human adipose‐derived stem cells (hASCs) were obtained from subcutaneous adipose tissue of healthy, adult, female donors (lean and obese) undergoing abdominal plastic surgery. The differences observed in proliferation, migration, and differentiation capacity in obese hASCs, compared with those of lean donors, at two different oxygen conditions, occurred in parallel with changes in cell surface markers, both under basal conditions and during differentiation. Obesity appears to be an important determinant of stem cell function independent of oxygen tension. 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 ± 1 kg/m2) and obese (n = 8; BMI: 35 ± 5 kg/m2). 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. Significance The obesity‐related hypoxic environment may have la