Huntington disease (HD) is an inherited late-onset neurological disorder characterized by progressive neuronal loss and disruption of cortical and basal ganglia circuits. Cell replacement using human embryonic stem cells may offer the opportunity to repair the damaged circuits and significantly ameliorate disease conditions. Here, we showed that in-vitro-differentiated human striatal progenitors undergo maturation and integrate into host circuits upon intra-striatal transplantation in a rat model of HD. By combining graft-specific immunohistochemistry, rabies virus-mediated synaptic tracing, and ex vivo electrophysiology, we showed that grafts can extend projections to the appropriate target structures, including the globus pallidus, the subthalamic nucleus, and the substantia nigra, and receive synaptic contact from both host and graft cells with 6.6 ± 1.6 inputs cell per transplanted neuron. We have also shown that transplants elicited a significant improvement in sensory-motor tasks up to 2 months post-transplant further supporting the therapeutic potential of this approach.

亨廷顿病（HD）是一种遗传性迟发性遗传疾病，其特征是进行性神经元丢失以及皮质和基底神经节回路的破坏。使用人类胚胎干细胞进行细胞置换可能提供修复受损电路并显着改善疾病状况的机会。在这里，我们显示了在HD大鼠模型中，体外分化的人类纹状体祖细胞会成熟并在纹状体内移植后整合到宿主电路中。通过结合移植物特异性免疫组织化学，狂犬病病毒介导的突触追踪和离体电生理学研究表明，移植物可以将投射物延伸至适当的靶标结构，包括苍白球，丘脑下核和黑质，并且可以从宿主细胞和移植物细胞获得突触接触，每个移植的神经元有6.6±1.6输入细胞。我们还表明，在移植后长达2个月的时间里，移植物引起的感觉运动功能有了显着改善，进一步支持了这种方法的治疗潜力。