Impairment in immunomodulatory function of mesenchymal stem cells from multiple myeloma patients.

BACKGROUND AND AIMS

Abnormality of immune regulation exists in multiple myeloma (MM). Mesenchymal stem cells (MSCs), a key regulator for immunomodulatory function, have decreased osteogenic potential in MM patients. Here we investigated the immunomodulatory function of MSCs from MM patients (MM-MSCs) and its relationship with decreased osteogenic potential.

METHODS

Real-time PCR was performed to detect the cytokines expressed in MM-MSCs (n = 22) and MSCs from normal donors (ND-MSCs, n = 11). Lymphocyte proliferative assay was used to detect the effect of MSCs on T cell proliferation. The effect of MSCs on T-cell cycle and T-cell activation markers expression were analyzed by flow cytometry. Flow cytometry and Western blot were used to detect apoptosis of T cells. Influence of T cells on osteogenic potential of MSCs was detected.

RESULTS

MM-MSCs exhibited increased expression of TGF-β1, IL-6, IL-3, TNF-α and RANKL and decreased expression of TGF-β2, TGF-β3 and FasL. The inhibitory effect of MM-MSCs on T.cell proliferative ability was attenuated. ND-MSCs silence more T cells in G0/G1 phase than MM-MSCs. The apoptosis-promoting effect of MM-MSCs on T cells seemed to be dampened. Expression of T-cell activation markers was significantly inhibited by ND-MSCs. T cells from normal donors possessed the ability to promote osteoblastic differentiation of ND-MSCs, but this ability of T cells both directly from MM patients and co-cultured with MM-MSCs was impaired.

CONCLUSIONS

MSCs from MM patients showed impaired immunoinhibitory capability on T cells, which in turn lose the ability to stimulate osteogenesis of MSCs.