The Effects Of Human Mesenchymal Stem Cells On Immune Response Of Mobilized Peripheral Blood Mononuclear Cells And In Human-mouse Chimera

Objectives To study the effect of huBM-MSCs on immune response of mobilized huPBMNCs and in human-NOD/SCID chimera. Methods 1 Mobilized huPBMNCs were cocultured with or without huBM-MSCs in presence or absence of PHA. PBMNCs proliferation, cell cycle, subtypes and cytokine secretion in supernatant were measured. 2 Mobilized human PBMNCs with or without huBM-MSCS were transplanted into sublethally irradiated NOD/SCID mice. The percentages of human CD45 and the phenotypes of human lymphocytes were measured Histopathology and immunophenotyping of organs were examined. Results 1 The "third party" BM-MSC inhibited PBMNC proliferation induced by PHA in a dose-dependent fashion and up-regulated the proportion of CD4⁺CD25⁺cells. In the presence of BM-MSCs, PBMNCs in proliferative phase S-G2-M decreased and the proportion of HLA-DR⁺ cells in response to PHA was significantly reduced. The presence of BM-MSCs in the cultures reduced the productions of various cytokines by cultured PBMNCs in response to PHA, but increased IL₁0 level in supernatant. 2 Most chimer showed the percentages of human CD45⁺ cells were above 25%. Engraftment of huCD45⁺ cells was associated with an acute X-GVHD syndrome mainly characterized by rapid and severe weight loss and pancytopenia. The liver and the lungs were the target organs. Human BM-MSCs 1×10⁶ improved weight loss associated with humen cells engraftment and did not cause to more severe pathologic lesion. Conclusions Human BM-MSCs may relieve the intensity of immune response, exerting a function of "immune homeostasis". Mobilized peripheral blood monocuclear cells 8 × 10⁷ are capable of engrafting into irradiated NOD/SCID mice with X-GVHD. There were no significant toxicities having been observed of coinfusion of huPBMNCs and allogeneic expanded huBM-MSCs. Coinfusion of huBM-MSCs has potential prevention and treatment of aGVHD.