Japanese researchers have used a genetic matching technique to successfully transplant retinal pigment cells derived from the stem cells of one monkey into the eyes of other monkeys without rejection or the need for immunosuppressant drugs. The team at the RIKEN Center for Developmental Biology (CDB) now hope the research will significantly improve the viability of human retinal cell transplant methods for curing age-related blindness caused by macular degeneration.

Japan is already well established as a leader in retinal degeneration research: this month alone (September 2016), it will host the XVIIth International Symposium on Retinal Degeneration (RD2016) in Kyoto, and the XXII Biennial Meeting of the International Society for Eye Research (ISER) in Tokyo. RIKEN’s Kobe-based CDB is home to a dedicated Laboratory for Retinal Regeneration. Researchers there have signed collaboration agreements with Kyoto University’s Center for iPS Cell Research and Application, Kobe City Medical Center General Hospital and Osaka University Hospital to push research in the field further.

The CDB team has already grown retinal pigment cells from induced pluripotent stem cells (iPSCs) and transplanted them into the damaged retina of a human participant, but these were autologous iPSCs created from the recipient’s own skin cells to avoid tissue rejection. This method, however, is costly and can take more than a year for cells to grow.

Lead author Dr Sunao Sugita of RIKEN said: “In order to make iPSC transplantation a practical reality, the current goal is to create banks of iPSC-derived tissues that can be transplanted into anyone as they are needed. However, immune responses and tissue rejection are big issues to overcome when transplanting tissue derived from other individuals.”

The new RIKEN research uses a technique known as Major histocompatibility complex (MHC) matching. MHCs are cell-surface proteins found in all cells that function in the immune system. After transplantation, if the MHCs of the transplanted cells are not recognised by the T cells of the host immune system, the tissue is rejected.

To test whether MHC matching is a viable method, the team used retinal pigment cells grown from monkey iPSCs in Kyoto University’s Center for iPS Cell Research and Application cell bank. They transplanted the cells into the subretinal space in monkeys and found that transplanted cells survived without rejection for at least six months in MHC-matched monkeys, without using any of the usually necessary immunosuppressant drugs. In contrast, rejection was relatively quick in MHC-mismatched monkeys.

Further examination in the laboratory of the MHC-matched cells showed that immune system T cells recognised the iPSC-derived retinal pigment cells and did not reject them. In a concurrent study, the researchers saw similar results when they repeated the experiment with human T cells and matched or unmatched retinal pigment cells grown from IPSCs.

Dr Sugita said: “Now that we have established the lack of immune response in monkeys and in human cells in vitro, using the iPS cell bank appears to be a viable solution, at least in the case of retinal pigment epithelial cell transplantation. 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 iPS cell bank is truly useful or not. If so, I think this type of transplantation can become standard treatment within five years.”


(via RIKEN and New Atlas)