We are very glad to answer two questions raised by Jitraruch etal. concerning our article.
Regarding the issue of “Do the authors have experimental data to show that human bone marrow mesenchymal stem cell (hBMSC)-derived hepatocytes did not trigger immune response in these animals?” Actually, we have no data concerning immune rejection, although many publications,1-4 including two references5, 6 cited by Jitraruch etal., have reported that hBMSCs have low inherent immunogenicity. hBMSC can inhibit proliferation and function of several major immune cells in vitro and in vivo. The recent report by Akiyama etal.7 demonstrated that BMSC-based immunotherapy involves coupling via Fas/Fas ligand (FasL) to induce T cell apoptosis.
Regarding the second question, the possible reason is that the D-galactosamine induced fulminant hepatic failure animals died within a very short time (within 96 hours). Furthermore, there must be many differences between clinical patients and animal models.
Following are the original conclusions and abstract in references cited by Jitraruch etal. These two references all indicated that BMSC has the characteristic of immune tolerance. The conclusion from the first reference is, “Undifferentiated and differentiated MSC do not elicit alloreactive lymphocyte proliferative responses and modulate immune responses. The findings support that MSC can be transplantable between HLA-incompatible individuals.”5
The abstract of the second reference mentions, “In vitro data suggest that MSCs have low inherent immunogenicity as they induce little, if any, proliferation of allogeneic lymphocytes. Instead, MSCs appear to be immunosuppressive in vitro. They inhibit T-cell proliferation to alloantigens and mitogens and prevent the development of cytotoxic T-cells. In vivo, MSCs prolong skin allograft survival and have several immunomodulatory effects, which are presented and discussed in the present study. Possible clinical applications include therapy-resistant severe acute graft-versus-host disease, tissue repair, treatment of rejection of organ allografts and autoimmune disorders.”6