Figure 7. MSCs infusions preserve in vitro cytotoxic T-lymphocyte (CTL) activity and prolong survival in alloBMT following in vivo leukemic challenge.

(A) MSCs do not interfere with ex vivo CTL-directed against P815 tumor cells. Allogeneic B6 T cells were stimulated in bulk by splenic-derived B6D2F1 DCs with or without hMSCs at a MSC-to-mTC ratio of 1:4. CTLs were subsequently isolated using Ficoll gradient and co-cultured with either P815 (H-2K^d) or EL4 (H-2K^b) tumor cell lines and cytolytic activity. Data are expressed as mean ± SEM and represent one of two similar, independent experiments. (B, C) MSC infusions preserve alloreactive graft-versus-leukemia (GvL) activity in alloBMT mice following P815 challenge as measured by survival (B) and minimal residual disease (MRD) using flow cytometry (C). Data from one of two independent experiments is shown. (n=8 to 16 mice per group; *p < 0.05 allo controls + P815 vs. allo + P815 + MSC by Mantel-Cox log-rank test). (D) GvL activity is preserved late post-transplant (D42) following hMSC infusions in allogeneic transplant mice challenged with P815 at lower T-cell doses (D70). AlloBMT mice received either one (1M) or two (2M) million B6 TCs on D0 and then 1M hMSCs or diluent only via tail-vein injection on D1 and D4. Representative FACS dot plots of H-2K^d-stained splenocytes from individual mice from two independent experiments are shown. Data for syngeneic mice were obtained at D14 given that syngeneic mice challenged with P815 uniformly die from tumor by D21.