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神经系统疾病，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替代可能会提供修复受损电路并显着改善疾病状况的机会。在这里，我们证明体外分化的人类纹状体祖细胞在 HD 大鼠模型中进行纹状体移植后会成熟并整合到宿主回路中。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，我们证明移植物可以将投射延伸到适当的目标结构，包括苍白球、丘脑底核和黑质，并接受突触接触来自宿主细胞和移植细胞，每个移植神经元有 6.6 ± 1.6 个输入细胞。我们还表明，移植后 2 个月内的感觉运动任务显着改善，进一步支持了这种方法的治疗潜力。