Umbilical Cord-derived Mesenchymal Stem Cells Instruct Monocytes Towards an IL10-producing Phenotype by Secreting IL6 and HGF

• Published in: Scientific reports Vol. 6; no. 1; p. 37566
• Main Authors: Deng, Yinan, Zhang, Yingcai, Ye, Linsen, Zhang, Tong, Cheng, Jintao, Chen, Guihua, Zhang, Qi, Yang, Yang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.12.2016; Nature Publishing Group
• Subjects: 13; 13/1; 13/21; 13/31; 631/250/127/1211; 631/250/127/1213; Antibodies; Bone marrow; Cell Communication; Cell Differentiation; Coculture Techniques; Cytokines; Dendritic Cells - cytology; Dendritic Cells - metabolism; Fetal Blood - cytology; Fetal Blood - metabolism; Flow cytometry; Gene Expression Regulation; Hepatocyte Growth Factor - genetics; Hepatocyte Growth Factor - immunology; Hepatocyte Growth Factor - metabolism; Hospitals; Humanities and Social Sciences; Humans; Immunogenicity; Immunology; Inflammation; Interleukin 1; Interleukin 10; Interleukin 6; Interleukin-10 - genetics; Interleukin-10 - immunology; Interleukin-10 - metabolism; Interleukin-6 - genetics; Interleukin-6 - immunology; Interleukin-6 - metabolism; Medical research; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mesenchyme; Monocytes; Monocytes - cytology; Monocytes - metabolism; multidisciplinary; Neutralization; Phenotype; Primary Cell Culture; R&D; Research & development; Science; Signal Transduction; Stem cells; Therapeutic applications; Umbilical cord
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep37566

Human UC-MSCs are regarded as an attractive alternative to BM-MSCs for clinical applications due to their easy preparation, higher proliferation and lower immunogenicity. However, the mechanisms underlying immune suppression by UC-MSCs are still unclear. We studied the mechanism of inhibition by UC-MSCs during the differentiation of monocytes into DCs and focused on the specific source and the role of the involved cytokines. We found that UC-MSCs suppressed monocyte differentiation into DCs and instructed monocytes towards other cell types, with clear decreases in the expression of co-stimulatory molecules, in the secretion of inflammatory factors and in allostimulatory capacity. IL6, HGF and IL10 might be involved in this process because they were detected at higher levels in a coculture system. UC-MSCs produce IL-6 and HGF, and neutralization of IL-6 and HGF reversed the suppressive effect of UC-MSCs. IL10 was not produced by UC-MSCs but was exclusively produced by monocytes after exposure to UC-MSCs, IL-6 or HGF. In summary, we found that the UC-MSC-mediated inhibitory effect was dependent on IL6 and HGF secreted by UC-MSCs and that this effect induced monocyte-derived cells to produce IL10, which might indirectly strengthen the suppressive effect of UC-MSCs.