Parkinson’s disease (PD) stands as the second most common neurodegenerative disorder after Alzheimer’s disease, and its prevalence continues to rise with the aging global population. Central to the pathophysiology of PD is the specific degeneration of midbrain dopamine neurons (mDANs) in the substantia nigra. Consequently, cell replacement therapy (CRT) has emerged as a promising treatment approach, initially supported by various open-label clinical studies employing fetal ventral mesencephalic (fVM) cells. Despite the initial favorable results, fVM cell therapy has intrinsic and logistical limitations that hinder its transition to a standard treatment for PD. Recent efforts in the field of cell therapy have shifted its focus towards the utilization of human pluripotent stem cells, including human embryonic stem cells and induced pluripotent stem cells, to surmount existing challenges. However, regardless of the transplantable cell sources (e.g., xenogeneic, allogeneic, or autologous), the poor and variable survival of implanted dopamine cells remains a major obstacle. Emerging evidence highlights the pivotal role of host immune responses following transplantation in influencing the survival of implanted mDANs, underscoring an important area for further research. In this comprehensive review, building upon insights derived from previous fVM transplantation studies, we delve into the functional ramifications of host immune responses on the survival and efficacy of grafted dopamine cells. Furthermore, we explore potential strategic approaches to modulate the host immune response, ultimately aiming for optimal outcomes in future clinical applications of CRT for PD.

帕金森病（PD）是继阿尔茨海默病之后第二大常见的神经退行性疾病，其患病率随着全球人口老龄化而持续上升。 PD 病理生理学的核心是黑质中脑多巴胺神经元 (mDAN) 的特异性变性。因此，细胞替代疗法（CRT）已成为一种有前景的治疗方法，最初得到了使用胎儿腹侧中脑（fVM）细胞的各种开放标签临床研究的支持。尽管最初取得了良好的结果，但 fVM 细胞疗法具有内在的和后勤上的局限性，阻碍了其向 PD 标准治疗的转变。细胞治疗领域最近的努力已将重点转向利用人类多能干细胞，包括人类胚胎干细胞和诱导多能干细胞，以克服现有的挑战。然而，无论可移植细胞来源如何（例如异种、同种异体或自体），植入的多巴胺细胞的较差且可变的存活率仍然是主要障碍。新的证据强调了移植后宿主免疫反应在影响植入 mDAN 存活方面的关键作用，强调了进一步研究的重要领域。在这篇全面的综述中，基于之前的 fVM 移植研究的见解，我们深入研究了宿主免疫反应对移植多巴胺细胞的存活和功效的功能影响。此外，我们探索调节宿主免疫反应的潜在战略方法，最终目标是在未来 CRT 治疗 PD 的临床应用中获得最佳结果。