Bone marrow-derived mesenchymal stem cells regulate the proliferation and activity of natural killer cells / 中国实验血液学杂志

ABSTRACT

This study was aimed to explore the effect of bone marrow-derived mesenchymal stem cells (MSC) on proliferation and activity of natural killer (NK) and NK-T cells. MSC was co-cultured with peripheral mononuclear cells from healthy donors in presence of IL-2, phytohemagglutinin (PHA) and mouse anti-human CD3 McAb (culture condition known to expand NK cells). The ratio of NK cells and NK-T cells was measured by flow cytometry and the effect of MSC on killing activity of NK cells against K562 cells was detected by MTT method after co-cultured with different densities of MSC. The results showed that MSC inhibited the production of NK cells in a dose-dependent manner generally. At the densities of 0, 1 × 10(5) and 5 × 10(5)/ml, the ratios of NK cells in the co-culture conditions were (16.9 ± 4.6), (14.0 ± 8.6) and (6.4 ± 4.6), respectively (P < 0.05). However, MSC could promote the formation of NK cells at lower MSC density (1 × 10(4)/ml), the ratio of NK cells reached to (20.9 ± 7.1), which was higher than that of culture condition without MSC (P < 0.05). The different densities of MSC in the co-culture conditions had no much influence on the ratio of NK-T cells (P > 0.05). MTT assay showed that the killing activity of suspended cells in co-culture system against K562 cells was parallel with the ratio of NK cells. Different densities of MSC regulated bidirectionally killing activity of NK to K562 cells by regulating bidirectionally ratio of NK cells. It is concluded that the MSC can promote the formation of NK cells and enhance its activity against tumor cells in the lower doses, while suppress the formation of NK cells and attenuate its tumor-killing effect in higher dose condition.