Human Mesenchymal Stem Cells Enhances the Growth of Acute Myeloid Leukemia Cells In Vivo.

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Human mesenchymal stem cells (MSC) are adhering cells capable of self-renew, proliferation and multilineage differentiation. MSC have the capacity to differentiate into osteoblasts, chondroblasts, myocytes and adipocytes when exposed to appropriate in vivo or in vitro stimuli. MSC descendants are involved in the formation of stroma maintaining the hemopoiesis. In this study, we investigated whether in vivo coinjection of hMSCs could enhance acute myeloid leukemia cells growth. Acute myeloid leukemia line (SHI-1) cells were grown in IMDM with 10%FCS. The hMSCs in adult BM were isolated and cultured in 60%DMEM (low glucose) and 40% MCDB-201 medium, 5%FCS, ITS+1. The hMSCs were immunotyped by using FACS. The differentiation ability in vitro towards osteoblasts and adipocytes was examined. BABL/c nude mice, aged 5 to 6 weeks, were used to explore the hMSCs' function in vivo. SHI-1cells and hMSCs were prepared either as single-cell type suspensions (3×106 cells in 100ul PBS) or a mixture of cells (3×106 SHI-1 cells plus 4×105 hMSCs in 100ul PBS ). Subcutaneous injection was performed in alar area. Injection of hMSCs alone was used as control. Mice were examined 3 times a week and tumor growth was evaluated by measuring the length and width of tumor mass. After 30 days, animals were sacrificed and tumor masses were weighed. Our experiments showed that the hMSCs have the potential of proliferation and the capacity to differentiate into osteoblasts and adipocytes in vitro. The immunophenotype of MSCs is CD34−,CD45−,CD105+,CD19−,CD13+,CD14−.10 days after injection with a mix of cells small tumor mass occurred in mice while no tumor mass could be observed in mice injected SHI-1 cells alone. Upon day 20, small tumor mass started to emerge in mice injected with SHI-1 cells alone. By the end of the experiment, mice were sacrificed and tumors were recovered. The weight of tumor masses from the mouse injected with mixed cells of SHI-1 and hMSCs was 0.42±0.18 g and from the mouse injected SHI-1 cells alone was 0.11±0.089 g, (P<0.01). No tumor masses could be found in mice injected with hMSCs alone. From this animal model, we proposed that human mesenchymal stem cells favors the growth of acute myeloid leukemia cells in vivo.