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

• Published in: Clinical and experimental immunology Vol. 176; no. 2; pp. 255 - 265
• Main Authors: Sempere, J. M., Martinez‐Peinado, P., Arribas, M. I., Reig, J. A., De La Sen, M. L., Zubcoff, J. J., Fraga, M. F., Fernández, A. F., Santana, A., Roche, E.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-05-2014; BlackWell Publishing Ltd
• Subjects: Adipose Tissue - cytology; Adipose Tissue - immunology; Adipose Tissue - metabolism; adult stem cells; CD3 Complex - immunology; CD3 Complex - metabolism; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; cell cloning; Cell Proliferation; Cells, Cultured; Clone Cells - cytology; Clone Cells - immunology; Clone Cells - metabolism; Cluster Analysis; Coculture Techniques; cytokine secretion; Cytokines - genetics; Cytokines - immunology; Cytokines - metabolism; DNA Methylation; Flow Cytometry; Humans; inflammation; Inflammation Mediators - immunology; Inflammation Mediators - metabolism; Interleukin-1beta - genetics; Interleukin-1beta - immunology; Interleukin-1beta - metabolism; Interleukin-4 - genetics; Interleukin-4 - immunology; Interleukin-4 - metabolism; Interleukin-5 - genetics; Interleukin-5 - immunology; Interleukin-5 - metabolism; Killer Cells, Natural - cytology; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - immunology; Mesenchymal Stromal Cells - metabolism; Original; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Transcriptome - genetics; Transcriptome - immunology; DNA-methylation; cytokine secretion; inflammation; cell cloning; adult stem cells
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/cei.12270

Summary
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.