Abstract
Mesenchymal stem cells (MSCs) are of special interest due their potential clinical use in cell-based therapy. Therapies engaging MSCs are showing increasing promise in the cancer treatment and anticancer drug screening applications. A multitude of growth factors and cytokines secreted from these cells are known to give such multifunctional properties, but details of their role are yet to be absolutely demonstrated. In this study, we have evaluated the influence of BMSCs on K562 cell line as chronic myeloid leukemia (CML) cells, with the use of a cytokine antibody array recognizing 34 cytokines. For this purpose, BMSCs were isolated and co-cultured with K562 cells; thereafter, cultured K562 alone and co-cultured K562 with BMSCs (10:1) were collected at day 7 and subjected to cell cycle distribution assay as well as annexin/PI analysis and Ki/caspase-3 assay for apoptosis assessment. In the following, the gene and protein expression levels of BAX and BCL-2 as pro- and anti-apoptotic agents were investigated. Furthermore, after 7 days’ treatment, culture medium was collected from both control and experimental groups for cytokine antibody array. It was found that BMSCs resulted in a robust increase in the number of cells at G0/G1 phase and arrest the G0/G1 phase as well as significantly inducing late apoptosis in K562 cells. The significant presence of TIMP-1 (tissue inhibitor of metalloproteinases-1), and moderate elevated signals for CINC-1 (cytokine-induced neutrophil chemoattractant-1) were obvious in the co-cultured conditioned media, but no significant increase was found in 32 other cytokines. It is concluded that co-culture of BMSCs with K562 cells could secrete a substantial amount of TIMP-1 and CINC-1. These cytokines could be involved in the inhibition of the K562 cell proliferation via BAX and caspase-3 cascade pathways.
Highlights
Mesenchymal stem cells (MSCs), which are present in adult organs and tissues such as heart, liver, kidney, adipose tissue, bone marrow, placenta, amniotic fluid, amnion, etc., are undifferentiated multipotential cells that have the capacity to differentiate into a broad range of different cell types, including osteocytes, adipocytes, chondrocytes, neuron-like cells and other connective tissues [1,2,3,4]
bone marrow derived-MSCs (BMSCs) like other MSCs had the capacity to adhere to culture plastic flasks, and morphologically, cells appear as spindle-shaped cells resembling fibroblasts (Fig 2A–2C)
There is still no clear information about the effect of MSCs on cancer cells, due to contradicting effects that could be favorable or unfavorable for cancer cell growth. This process is complicated by cellular interactions between MSCs and cancer cells that include membrane fusion, metabolites or growth factors that shape the relationship of MSCs with tumor cells
Summary
Mesenchymal stem cells (MSCs), which are present in adult organs and tissues such as heart, liver, kidney, adipose tissue, bone marrow, placenta, amniotic fluid, amnion, etc., are undifferentiated multipotential cells that have the capacity to differentiate into a broad range of different cell types, including osteocytes, adipocytes, chondrocytes, neuron-like cells and other connective tissues [1,2,3,4]. Fibroblasts as normal stroma, are predominant cells that secrete an extracellular matrix (ECM) providing a natural barrier against tumor progression [11] In these processes, MSCs can be basic. It was shown that in the presence of cancer cells, MSCs do not differentiate in vitro or facilitate the tumor angiogenesis in vivo These results opening interesting new scenarios in the relationship between cancer and stem cells. These findings may lead to greater caution, when managing autologous fat grafts in cancer patients [13] With these explanations, the aim of this study was to explore the influence of BMSCs on proliferation and apoptosis of K562 cell line as chronic myeloid leukemia (CML) cells via investigation of secreted cytokines. At the end of the 7th day, supernatant of the two groups of cells was collected for cytokine antibody array
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