| Mesenchymal stem cell (MSC) can inhibit lymphocyte proliferation through direct cell-cell contact and cytokine secretion. The co-transplantation of cultured MSC and hematopoietic stem cells is potentially useful for the prevention and treatment of GVHD. Previous data have also demonstrated that hepatocyte growth factor (HGF), a peliotropic cytokine of mesenchymal origin promoting migration, proliferation and survival in a wide spectrum of cells, has immunoregulatory activity by suppressing the maturation and development of monocytes into dendritic cells. Thus, HGF may inhibit the ongoing alloimmune reaction and promote repair of thymus epithelial damage by irradiation, resulting in the alleviation of GVHD severity while remaining GVL effect. To identify if the immune synergistic effect of MSC and HGF exists, we investigated immunoregulatory function of Ad-HGF modified MSC (MSC-HGF). In this context, we found that the intrinsic property and biological behavior of MSC-HGF were unchanged, suggesting of the feasibility and exploitability of this gene modification strategy. Then, we investigated the immunoregulatory function of MSC-HGF both in vitro and in vivo. The results showed that MSC-HGF exhibit more potently suppressive activity than MSC on the lymphocyte proliferation elicited by Con A or allogeneic cellular stimuli. More importantly, MSC-HGF administration prolonged the mean survival time of skin grafting across MHC barrier (C57→BALB/c) than MSC alone. These findings support the useful potentiality of MSC-HGF in controlling GVHD in the settings of allogeneic HSCT.In this study, human MSC derived from bone marrow were isolated and culture-expanded by Percoll density gradient centrifugation and their property of adherence to plastic flasks. Mouse compact bone derived MSC were gained by culture of collagenase type II digested bone debris as previously described. The adherent cells displayed themselves as fibroblast-like in morphology. Flow cytometric analysis...
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