Single cell-derived clones from human adipose stem cells present different immunomodulatory properties

Abstract

Human adipose mesenchymal stem cells are a heterogeneous population, where cell cultures derived from single‐cell‐expanded clones present varying degrees of differential plasticity. This work focuses on the immunomodulatory/anti‐inflammatory properties of these cells. To this end, five single‐cell clones were isolated (generally called 1.X and 3.X) from two volunteers. Regarding the expression level of the lineage‐characteristic surface antigens, clones 1·10 and 1·22 expressed the lowest amounts, while clones 3·10 and 3·5 expressed more CD105 than the rest and clone 1·7 expressed higher amounts of CD73 and CD44. Regarding cytokine secretion, all clones were capable of spontaneously releasing high levels of interleukin (IL)‐6 and low to moderate levels of IL‐8. These differences can be explained in part by the distinct methylation profile exhibited by the clones. Furthermore, and after lipopolysaccharide stimulation, clone 3.X produced the highest amounts of proinflammatory cytokines such as IL‐1β, while clones 1·10 and 1·22 highly expressed IL‐4 and IL‐5. In co‐culture experiments, clones 1.X are, together, more potent inhibitors than clones 3.X for proliferation of total, CD3+T, CD4+T and CD8+T lymphocytes and natural killer (NK) cells. The results of this work indicate that the adipose stem cell population is heterogeneous in cytokine production profile, and that isolation, characterization and selection of the appropriate cell clone is a more exact method for the possible treatment of different patients or pathologies.