The biology of vitamin D3 is well defined, as are the effects of its active metabolites on various cells, including mesenchymal stromal/stem cells (MSCs). However, the biological potential of its precursor, cholecalciferol (VD3), has not been sufficiently investigated, although its significance in regenerative medicine—mainly in combination with various biomaterial matrices—has been recognized. Given that VD3 preconditioning might also contribute to the improvement of cellular regenerative potential, the aim of this study was to investigate its effects on bone marrow (BM) MSC functions and the signaling pathways involved. For that purpose, the influence of VD3 on BM-MSCs obtained from young human donors was determined via MTT test, flow cytometric analysis, immunocytochemistry, and qRT-PCR. Our results revealed that VD3, following a 5-day treatment, stimulated proliferation, expression of pluripotency markers (NANOG, SOX2, and Oct4), and osteogenic differentiation potential in BM-MSCs, while it reduced their senescence. Moreover, increased sirtuin 1 (SIRT1) expression was detected upon treatment with VD3, which mediated VD3-promoted osteogenesis and, partially, the stemness features through NANOG and SOX2 upregulation. In contrast, the effects of VD3 on proliferation, Oct4 expression, and senescence were SIRT1-independent. Altogether, these data indicate that VD3 has strong potential to modulate BM-MSCs’ features, partially through SIRT1 signaling, although the precise mechanisms merit further investigation.

Mesenchymal stem cells from human adipose tissue (hASCs) are proposed as suitable tools for soft tissue engineering and reconstruction. Although it is known that hASCs have the ability to home to sites of inflammation and tumor niche, the role of inflammatory cytokines in the hASCs‐affected tumor development is not understood. We found that interferon‐γ (IFN‐γ) and/or tumor necrosis factor‐α (TNF‐α) prime hASCs to produce soluble factors which enhance MCF‐7 cell line malignancy in vitro. IFN‐γ and/or TNF‐α‐primed hASCs produced conditioned media (CM) which induced epithelial to mesenchymal transition (EMT) of MCF‐7 cells by reducing E‐Cadherin and increasing Vimentin expression. Induced EMT was accompanied by increased invasion, migration, and urokinase type‐plasminogen activator (uPA) expression in MCF‐7 cells. These effects were mediated by increased expression of transforming growth factor‐β1(TGF‐β1) in cytokines‐primed hASCs, since inhibition of type I TGF‐β1 receptor on MCF‐7 cells and neutralization of TGF‐β1 disabled the CM from primed hASCs to increase EMT, cell migration, and uPA expression in MCF‐7 cells. Obtained data suggested that IFN‐γ and/or TNF‐α primed hASCs might enhance the malignancy of MCF‐7 cell line by inducing EMT, cell motility and uPA expression in these cells via TGF‐β1‐Smad3 signalization, with potentially important implications in breast cancer progression. © 2016 IUBMB Life, 68(3):190–200, 2016