A critical review summarizing the history, current status, and misconceptions of dopamine cell replacement therapy for Parkinson’s disease, from fetal grafts to stem cell-derived vmDA neuron transplants now entering clinical trials.

Offers translationally relevant synthesis on stem-cell-derived dopamine replacement—highlighting clinical progress, safety issues, and pitfalls—which can inform trial design, risk mitigation, and therapeutic strategy in PD drug development.

Parkinson's disease (PD) is a common neurodegenerative disorder associated with the accumulation of alpha-synuclein in Lewy bodies and Lewy neurites, as well as cell loss, including ventral midbrain dopaminergic (vmDA) neurons in the substantia nigra. This degeneration is responsible for some of the characteristic motor features of PD, which, in the early stages of the disease, can be successfully treated pharmacologically. However, in later stages of the disease, the efficacy of these drugs declines, and they can cause side effects. Dopamine cell therapy, which involves replacing lost vmDA neurons by implanting new exogenous ones, is a promising alternative. While research on dopamine cell therapies has made substantial progress over the last few decades, from early foetal transplants to stem cell-derived transplants currently in clinical trials, it is also susceptible to potential misconceptions. This review summarises the past, present, and future of this therapeutic strategy whilst also discussing these potential misconceptions. In doing so, the status of dopamine cell therapy for PD will be critically summarised.