Induced Pluripotent Stem Cells (iPSCs) as a Regenerative Strategy for Parkinson's Disease: Opportunities and Challenges.

Parkinson’s disease (PD) is a chronic and progressively debilitating neurodegenerative condition marked by the gradual depletion of dopaminergic neurons within the substantia nigra. This neuronal loss manifests as a spectrum of motor dysfunctions and non-motor disturbances that profoundly affect daily functioning and overall quality of life. Current clinical interventions, including levodopa administration and deep brain stimulation, largely target symptom management rather than addressing the underlying neurodegenerative processes, thereby offering only temporary relief. In light of these limitations, there has been growing interest in regenerative approaches aimed at restoring neuronal function. Among these, induced pluripotent stem cells (iPSCs) have revolutionized the field, enabling the reprogramming of patient-derived somatic cells into pluripotent states that can subsequently be differentiated into functional dopaminergic neurons. Beyond their therapeutic potential for cell replacement, iPSCs also provide an invaluable platform for modeling disease mechanisms and evaluating novel treatment strategies. iPSCs enable patient-specific disease modelling and physiologically relevant drug screening. Preclinical evidence demonstrates that transplantation of iPSC-derived dopaminergic neurons can restore motor function, while support the feasibility and short-term safety. Nevertheless, significant challenges remain, including tumorigenicity risk, differentiation variability, graft integration challenges, and economic, regulatory, and ethical issues. With the advancement of innovations including gene editing, brain organoids, and multimodal approaches, iPSCs hold great promise to revolutionize Parkinson’s therapy toward safer, more effective, and personalized precision medicine. Unlike previous reviews, this article integrates mechanistic insights, translational barriers, and future technological directions, offering a focused perspective on how iPSC-based strategies may be realistically advanced toward clinical application.