title: Increasing proliferation of murine adipose tissue-derived mesenchymal stem cells by TNF-α plus IFN-γ.
abstract: The objective of the current study was to assess the effects of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) along with their simultaneous application on proliferation and pluripotency genes of murine adipose tissue-derived mesenchymal stem cells (AT-MSCs). The proliferation, doubling time (DT), colony-forming unit-fibroblast (CFU-F), pluripotency genes expression, and proliferation-related immunomodulatory markers of MSCs were analyzed upon activation with TNF-α (10 ng/ml), IFN-γ (10 ng/ml) and both TNF-α and IFN-γ (5 ng/ml + 5 ng/ml). Pluripotency genes including Oct-4, Sox-2, and Nanog as well as proliferation-associated immunomodulatory cytokines such as insulin-like growth factor 1 (IGF-1) and transforming growth factor-β (TGF-β) expression were evaluated using real-time PCR. Surface expression of Qa2 (HLA-G) was analyzed by flow cytometry. Pretreatment of MSCs with TNF-α plus IFN-γ led to significantly increased proliferation, DT and CFU-F as well as expression of pluripotency genes in AT-MSCs (p < 0.01). MSCs expressed more IGF-1, TGF-β, and Qa2 upon activation with TNF-α plus IFN-γ and IFN-γ. MSCs expressed significantly decreased amounts of TGF-β and Qa2 in presence of TNF-α. TNF-α combined with IFN-γ may be improved the proliferation of AT-MSCs. Conversely, expanded MSCs pointed out low levels of the immunomodulatory marker, s especially Qa2 in the presence of TNF-α. In conclusion, we showed that TNF-α together with IFN-γ increased the proliferation of MSCs and slightly enhanced the expression of pluripotency genes.
authors.affiliation: a Department of Immunology , Faculty of Medical Sciences, Tarbiat Modares University , Tehran , Iran .
authors.forename: Hemn
authors.initials: H
authors.lastname: Mohammadpour
authors.affiliation: a Department of Immunology , Faculty of Medical Sciences, Tarbiat Modares University , Tehran , Iran .
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Pourfathollah
authors.affiliation: b High Institute for Research and Education in Transfusion Medicine, Blood Transfusion Research Center , Tehran , Iran , and.
authors.forename: Mahin
authors.initials: M
authors.lastname: Nikougoftar Zarif
authors.affiliation: c Department of Immunology , School of Medicine, Shahid Beheshti University of Medical Sciences , Tehran , Iran.
authors.forename: Sayed Mahmoud
authors.initials: SM
authors.lastname: Hashemi
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects* / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D007371:Interferon-gamma / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: C000611649:IFNG protein, mouse; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: IFN-γ; TNF-α; mesenchymal stem cells; pluripotency; proliferation