In order for GVHD
to occur, the donor graft must contain immune-competent T cells, be transplanted into a recipient unable to mount a successful immune response against the graft, and the recipient must express tissue antigens not present in the donor transplant . The standard first-line therapy for Decitabine aGVHD focuses on the suppression of donor T cells through the administration of glucocorticosteroids combined with immunosuppressive drugs, such as cyclosporin A or tacrolimus . Steroid therapies have improved the outcome and increased survival of many patients with aGVHD [5-7]. Nevertheless, the prognosis for steroid refractory aGVHD patients remains very poor, with a 5-year survival rate as low as 30% [2, 8]. In these cases, a second-line therapy
is required. Mesenchymal stem or stromal cells (MSC) are a heterogeneous pericyte-like cell population present in bone marrow, adipose, cord blood and other tissues [9, 10]. MSC form plastic adherent colonies in vitro and are capable of osteocyte, adipocyte and chondrogenic differentiation [11, 12]. These cells are potential agents for regenerative medicine , and act through the secretion of ‘trophic factors’ that promote repair through the recruitment and activation of other reparative cells. MSC may also act through cytoprotective mechanisms or by immune suppression [13, 14]. In vitro, MSC have a direct suppressive effect on T and B lymphocytes, natural killer (NK) cells and supporting dendritic cell (DC) functions [15-21]. The combination of immunoregulatory and regenerative properties BVD-523 in vitro suggest a potential role
for MSC in the therapeutic induction of immune tolerance. To this effect, there has been interest in the use of MSC as a cell therapy for a number of inflammatory conditions, such as Crohn’s disease, multiple sclerosis and aGVHD [22-25]. Autologous and Exoribonuclease allogeneic ex-vivo expanded human MSC have been utilized in studies of haematological disorders, with promising results. Le Blanc et al. demonstrated the potential for MSC infusion to treat steroid-refractory GVHD of the gut and liver, showing no reactivity between the haploidentical MSC and recipient lymphocytes , and this was extended to MSC from mismatched unrelated donors . However, the initial optimism for MSC as a cell therapy for aGVHD has become tempered by recent clinical trials. While MSC proved safe and beneficial following infusion to patients with aGVHD in a Phase II trial , a Phase III trial for steroid-refractory aGVHD demonstrated no statistical difference between MSC or the placebo groups in relation to achievement of complete response within 28 days of initiating treatment [27, 28]. However, it is important to note that beneficial effects were observed in this Phase III study for the treatment of aGVHD of the gut and liver, but not of the skin.