Deep brain stimulation (DBS), a cornerstone neurosurgical intervention for advanced Parkinson's disease, exerts modulatory effects on aberrant basal ganglia circuitry through continuous high- frequency electrical stimulation. This approach yields sustained amelioration of motor symptoms while concurrently reducing the requisite dosage of dopaminergic pharmacotherapy. Nonetheless, DBS still has its limitations: its efficacy on non-motor symptoms remains limited, electrode implantation leads to biological reactions, and it cannot alter the trajectory of disease progression. Embryonic stem cells and induced pluripotent stem cells can be directed to differentiate into functionally mature nigrostriatal dopaminergic neurons, demonstrating the potential for neuronal replacement and neuroprotective effects in preclinical models and early-phase clinical trials. Mesenchymal stem cells and their derived exosomes mitigate neuroinflammation and impede α-synuclein aggregation through neurotrophic support and immunomodulatory mechanisms. This article reviews two core domains that have achieved breakthroughs in the treatment of Parkinson's disease—DBS and stem cells—and covers their current status and future prospects. First, this review elucidates the therapeutic mechanisms of DBS, including neurotransmitter release regulation and neuroinflammation suppression, while evaluating its long-term efficacy (e.g., the sustainability of motor improvement and advancements in directional stimulation technology) and safety challenges (e.g., cognitive impairment, mood disturbances, and glial scar formation induced by electrode implantation). Second, it provides an in-depth analysis of the differentiation mechanisms of stem cells from different sources (embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, etc.), preclinical efficacy validation, and early-phase clinical trial outcomes (e.g., the long-term safety and motor function enhancement observed in the transplantation of induced pluripotent stem cell- derived nigrostriatal dopaminergic progenitor cells). Third, the article addresses the standardization of stem cell therapy protocols, strategies for managing immune rejection, and current international regulatory and ethical frameworks. The core challenges of current Parkinson's disease treatment paradigms are as follows: DBS shows limited efficacy in improving axial symptoms (e.g., freezing of gait), whereas stem cell transplantation faces issues such as low long-term graft survival and insufficient functional integration. Looking ahead, multidisciplinary integration is essential to promote the synergistic application of DBS and stem cell therapy, develop personalized treatment protocols under the guidance of precision medicine, and translate novel neural interface materials and genetic engineering technologies into clinical practice. Ultimately, such integrated strategies hold the promise of advancing Parkinson's disease therapy from mere symptom control to true disease modification.
Liang et al. (Fri,) studied this question.