Immune Tolerance Achieved in iPS Cell-Derived Neural Transplants for Parkinson's Disease

A groundbreaking clinical study has demonstrated that allogeneic induced pluripotent stem cell (iPSC)-derived dopaminergic neural progenitors can be transplanted into Parkinson's disease patients with minimal immune rejection. Led by researchers at Kyoto University, the trial involved seven participants who received bilateral brain transplants of these specialized cells. The cells were derived from a single, clinical-grade iPSC line with a common HLA haplotype, and some recipients had HLA-matched transplants while others were mismatched, mimicking real-world donor compatibility scenarios.

Participants were given moderate immunosuppressive therapy with tacrolimus for up to 15 months post-surgery. Throughout the follow-up period, no significant immune responses or adverse events related to immunosuppression were observed. Advanced PET imaging and serum analyses showed no signs of neuroinflammation or inflammatory responses, even after immunosuppressant withdrawal. Further immune testing revealed that the transplanted cells elicited minimal T cell activation, indicating a high level of immune tolerance.

This research provides compelling evidence that the brain's unique immune environment, combined with the low immunogenicity of iPSC-derived grafts, can support successful transplantation even when donor cells are HLA mismatched. These findings suggest that less intensive immunosuppressive regimens may suffice for future regenerative treatments in Parkinson's disease. Moreover, the use of iPSC technology offers advantages over traditional fetal tissue transplantation, including consistency, scalability, and fewer ethical concerns. The development of hypoimmunogenic or universal iPSC lines through gene editing techniques could further reduce the need for immunosuppression, paving the way for more accessible and safer therapies for neurodegenerative conditions.

The study underscores the importance of personalized immune monitoring to optimize transplantation outcomes and highlights the potential for iPSC-based cell therapies to revolutionize the treatment landscape for Parkinson's disease and other central nervous system disorders.

Source: https://medicalxpress.com/news/2025-08-immune-tolerance-ips-cell-derived.html