Selection of donor and recipient
Cells transplantation is greatly different from organ transplantation, in which the transplanted cells are always in a hypoxic environment, which accelerates the process of graft fibrosis, devitalization, and necrosis. Therefore, scholars start to search the hypoxia tolerance cells as a donor which can preserve long-term viability in hypoxic condition. Class fish has wide distribution and is large in quantity. Because of living in the hypoxia environment for a long time, the fish has a higher ability to adapt hypoxic condition than mammalian. It will resolve the shortage problem of donor if the fish liver can be used as a source of cells transplantation. Zhao et al[4-5] transplanted the tilapia pancreatic islet cells into the diabetic mouse and found that blood glucose level was decreased. Study findings demonstrated that the tilapia pancreatic islet cells were easy to isolate and preserve their function, as well as the ability to tolerance the hypoxic environment. Therefore, we presume that the fish hepatocyte grafts could reverse mammalian liver function failure.

Cell-mediated immune response of tilapia-to-rat hepatocyte xenotransplantation
CD4+ and CD8+ T cells are the main immunocytes that mediate cellular immune response. Histological observation revealed that only a few hours after tiplapia hepatocytes transplantation into the rat spleen, there were a lot of inflammatory cells invaded the area surrounding the graft. The inflammatory cell infiltration became more and more obvious at 8 hours after transplantation, and at the same time, hepatocytes began to deteriorate, even necrosis. CD4+ and CD8+ cells surrounding the graft were observed using immunohistochemical SABC methods after tilapia hepatocytes transplantation into the rat spleen. In addition, the aggregation of CD4+ and CD8+ T cells occurred surrounding the graft at 4 hours after transplantation, and this phenomenon became more obvious at 8 hours. These findings indicate that cell response may play an important role in the early stage of transplantation. The rejection occurs at a few hours after transplantation rather than a few minutes or a few days.
During xenotransplantation, great difference of major histocompability complex molecule between donor and recipient leads to difficult direct presentation of major histocompability complex antigen between donor and recipient, so the indirect presentation become a dominant process[6]. The xenogeneic antigen is first recognized by assistant reaction cells, and then presented to T cells. CD4+ and CD8+ T cells-mediated immune response was induced through this indirect pathway[7]. T cell-mediated immune response consists of two basic ways: the first one is CD8+ T cell reacting as a cytotoxic T-cell which has specific function of cytolysis, and the other one is the inflammatory reaction that is mediated by CD4+ T cell as a hypersensitive T-cell and associated with dominant infiltration by monocyte. Because of xenogeneic antigen processing, cytokine synthesis and excretion, and T cell activation and amplification, a few days are needed for cell-mediated rejection. Wright et al[8] reported that CD4+ and CD8+ T cells were observed in the area surrounding the graft at 3 days after transplantation of tilapia islet cells to diabetes mellitus. Dickson et al[9] transplanted tilapia islet cells microencapsulated with alginate into diabetes mellitus mouse body and blocked CD4+, CD8+ T cells using monoclonal antibodies. Results showed that the survival time of grafts was obviously prolonged.
In the present study, CD4+ and CD8+ cell aggregation was observed a few hours after tilapia hepatocytes transplantation into the rat spleen. This may be due to the following factors: ① The normal spleen contains large amount of T cells, B cells, natural killer cells, etc., especially more CD4+, CD8+ T cells and antigen-presenting cells disseminated in the splenic pulp[10]. After hepatocytes were transplanted into the spleen, because of limited space and distance, slpenic antigen presenting cells can recognize, contact, and capture the foreign antigen quickly, and present to T cells for producing effective immune response to induce cell-mediated immune response[11]. ② Some natural killer cells are CD4+ and CD8+ cells[10], so the CD4+ and CD8+ cells appearing in the area surrounding the grafts in the early stage of transplantation are natural killer cells rather than T cells, but are “innate T cells”.
It has been reported that when the xenogenic islet cells were transplanted across the wide piece barrier, such as fish-to-mammalian, the graft will be destroyed immediately by a process called instant blood-mediated inflammatory reaction.