Developmental and Regenerative Neurobiology, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Lund, Sweden.
Lund Stem Cell Center, Lund University, Lund, Sweden.
Nat Rev Neurosci. 2020 Feb;21(2):103-115. doi: 10.1038/s41583-019-0257-7. Epub 2020 Jan 6.
Cell-replacement therapies have long been an attractive prospect for treating Parkinson disease. However, the outcomes of fetal tissue-derived cell transplants in individuals with Parkinson disease have been variable, in part owing to the limitations of fetal tissue as a cell source, relating to its availability and the lack of possibility for standardization and to variation in methods. Advances in developmental and stem cell biology have allowed the development of cell-replacement therapies that comprise dopamine neurons derived from human pluripotent stem cells, which have several advantages over fetal cell-derived therapies. In this Review, we critically assess the potential trajectory of this line of translational and clinical research and address its possibilities and current limitations and the broader range of Parkinson disease features that dopamine cell replacement based on generating neurons from human pluripotent stem cells could effectively treat in the future.
细胞替代疗法长期以来一直是治疗帕金森病的一种有吸引力的方法。然而，在帕金森病患者中，源自胎儿组织的细胞移植的结果存在差异，部分原因是胎儿组织作为细胞来源存在局限性，包括其可用性、缺乏标准化的可能性以及方法的变化。发育和干细胞生物学的进步使得基于人多能干细胞的多巴胺神经元的细胞替代疗法得以发展，这种疗法比源自胎儿细胞的疗法具有多种优势。在这篇综述中，我们批判性地评估了这一转化和临床研究路线的潜在轨迹，并探讨了其可能性、当前的局限性以及基于人多能干细胞产生神经元的多巴胺细胞替代疗法未来可能有效治疗的更广泛的帕金森病特征。
