Effects of indoleamine 2, 3‐dioxygenase (IDO) silencing on immunomodulatory function and cancer‐promoting characteristic of adipose‐derived mesenchymal stem cells (ASCs)

• Published in: Cell biology international 2021-12, Vol.45 (12), p.2544-2556
• Main Authors: Heidari, Fahimeh, Razmkhah, Mahboobeh, Razban, Vahid, Erfani, Nasrollah
• Format: Article
• Language: English
• Subjects: adipose derived mesenchymal stem cell; Adipose tissue; Adipose Tissue - drug effects; Adipose Tissue - metabolism; Adult; Cancer; Cell Movement - drug effects; Cell proliferation; Cell Proliferation - drug effects; Cells, Cultured; Cytokines; Dioxygenase; Female; Flow cytometry; Growth factors; Hepatocyte growth factor; Humans; Immunologic Factors - metabolism; Immunomodulation; Immunoregulation; immunosuppression; Indoleamine 2, 3‐dioxygenase; Indoleamine-Pyrrole 2,3,-Dioxygenase - pharmacology; Interferon; Interferon-gamma - metabolism; Leukocyte migration; Lymphocytes; Lymphocytes - drug effects; Lymphocytes - metabolism; Lymphocytes T; Mesenchymal stem cells; Mesenchymal Stem Cells - drug effects; Middle Aged; Neoplasms - drug therapy; Neoplasms - metabolism; Peripheral blood; Phenotypes; regulatory T cell; siRNA; Stem cells; Stromal cells; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - metabolism; Tryptophan; Tumor cell; Tumor cells; Young Adult
• ISSN: 1065-6995; 1095-8355
• DOI: 10.1002/cbin.11698

Indoleamine 2, 3‐dioxygenase (IDO) catabolizes tryptophan, mediates immunomodulatory functions, and is released by stromal cells such as mesenchymal stem cells. The aims of this study were to investigate the effects of IDO silencing on immunosuppressive function of adipose‐derived mesenchymal stem cells (ASCs), T cells phenotype, and the proliferation/migration of tumor cells. ASCs isolated from adipose tissues of healthy women were transfected with IDO‐siRNA. Galectin‐3, transforming growth factor‐β1, hepatocyte growth factor, and interleukin‐10 as immunomodulators were measured in ASCs using qRT‐PCR. T cells phenotype, interferon‐γ, and interleukin‐17 expression were evaluated in peripheral blood lymphocytes (PBLs) cocultured with IDO silenced‐ASCs by flow cytometry and qRT‐PCR, respectively. Scratch assay was applied to assess the proliferation/migration of MDA‐MB‐231 cell line. Galectin‐3 was upregulated (p ˂ 0.05) while hepatocyte growth factor was downregulated (p ˂ 0.05) in IDO‐silenced ASCs compared to control groups. Regulatory T cells were inhibited in PBLs cocultured with IDO‐silenced ASCs; also T helper2 was decreased in PBLs cocultured with IDO‐silenced ASCs relative to the scramble group. IDO‐silenced ASCs caused interferon‐γ overexpression but interleukin‐17 downregulation in PBLs. The proliferation/migration of MDA‐MB‐231 was suppressed after exposing to condition media of IDO‐silenced ASCs compared with condition media of untransfected (p