Department of Neurological Surgery and Weill Institute of Neuroscience, University of California, 513 Parnassus Ave, Health Science East, E840, San Francisco, CA, 94143, USA.
Sci Rep. 2024 Feb 13;14(1):3610. doi: 10.1038/s41598-024-52478-6.
Interneuron progenitor transplantation can ameliorate disease symptoms in a variety of neurological disorders. The strategy is based on transplantation of embryonic medial ganglionic eminence (MGE) progenitors. Elucidating how host brain environment influences the integration of interneuron progenitors is critical for optimizing this strategy across different disease states. Here, we systematically evaluated the influence of age and brain region on survival, migration, and differentiation of transplant-derived cells. We find that early postnatal MGE transplantation yields superior survival and more extensive migratory capabilities compared to transplantation during the juvenile or adult stages. MGE progenitors migrate more widely in the cortex compared to the hippocampus. Maturation to interneuron subtypes is regulated by age and brain region. MGE progenitors transplanted into the dentate gyrus sub-region of the early postnatal hippocampus can differentiate into astrocytes. Our results suggest that the host brain environment critically regulates survival, spatial distribution, and maturation of MGE-derived interneurons following transplantation. These findings inform and enable optimal conditions for interneuron transplant therapies.
神经前体细胞移植可以改善多种神经紊乱疾病的症状。该策略基于胚胎内侧神经节隆起(MGE)前体细胞的移植。阐明宿主大脑环境如何影响神经前体细胞的整合对于优化不同疾病状态下的这种策略至关重要。在这里,我们系统地评估了年龄和大脑区域对移植来源细胞的存活、迁移和分化的影响。我们发现,与在幼年或成年阶段进行移植相比,早期 postnatal MGE 移植可获得更好的存活和更广泛的迁移能力。MGE 前体细胞在皮质中的迁移范围比海马体更广。成熟为不同的中间神经元亚型受年龄和大脑区域的调节。移植到早期 postnatal 海马齿状回亚区的 MGE 前体细胞可以分化为星形胶质细胞。我们的结果表明,宿主大脑环境在移植后对 MGE 衍生的中间神经元的存活、空间分布和成熟具有关键调节作用。这些发现为中间神经元移植治疗提供了信息和优化条件。