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Japanese researchers see retinal transplant success in MHC-matched monkeys

Prior to the current study, the researchers had started a clinical transplant trial in people with age-related macular degeneration. These trials used retinal pigment cells from autologous induced pluripotent st cells (iPSCs) – st cells created from the recipient’s own skin cells – to avoid tissue rejection.However, while the method was effective, it was said that producing the autologous iPSCs was costly and took time, meaning patients had to wait more than a year for a transplant.Lead author Dr Sunao Sugita said creating banks of iPSC-derived tissues would make iPSC transplantation a practical reality, but noted that adverse immune responses continued to be a major issue.{{quote-A:R-W:450-Q: If the MHCs of transplanted cells are not recognised by the T cells of the host immune syst, there is an immune response and the tissue is rejected. }}The latest study tested a technique called MHC matching as a way to overcome this issue. Major histocompatibility complexes (MHCs) are sets of cell-surface proteins found in all cells that function in the immune syst.In humans, MHCs are also called human leukocyte antigens (HLAs). If the MHCs of transplanted cells are not recognised by the T cells of the host immune syst, there is an immune response and the tissue is rejected.Using retinal pigment cells grown from monkey iPSCs in the iPSC bank at the Center for iPS Cell Research and Application, Kyoto University, the researchers conducted the transplant procedure in monkeys with either genetically matched or non-matched MHCs.Transplanted cells were found to survive without rejection for at least six months in MHC-matched monkeys without the use of immunosuppressant drugs, while rejection was relatively quick in MHC-mismatched monkeys.Immunohistochical examination showed infiltration by inflammatory cells was only present in the transplanted grafts of MHC-mismatched monkeys. In vitro, the team saw that T cells failed to respond to the iPSC-derived retinal pigment cells if they were from an MHC-matched monkey.The researchers had similar results in a separate study when they repeated the experiment with human T cells and HLA-matched or unmatched retinal pigment cells grown from IPSCs.Dr Sugita said these findings suggested that using an iPSC bank was a viable solution, adding, “In the next clinical trial, we plan to use allogeneic iPS-retinal pigment epithelial cells from HLA homozygote donors.The clinical data after the transplantation will allow us to see if the iPSC bank is truly useful or not. If so, I think this type of transplantation can become standard treatment within five years.”