Laboratoire de Neurosciences Expérimentales et Cliniques, Inserm, Université de Poitiers, 86022 Poitiers, France.
CHU de Poitiers, 86022 Poitiers, France.
Cells. 2022 Apr 1;11(7):1191. doi: 10.3390/cells11071191.
Intrastriatal embryonic ventral mesencephalon grafts have been shown to integrate, survive, and reinnervate the host striatum in clinical settings and in animal models of Parkinson's disease. However, this ectopic location does not restore the physiological loops of the nigrostriatal pathway and promotes only moderate behavioral benefits. Here, we performed a direct comparison of the potential benefits of intranigral versus intrastriatal grafts in animal models of Parkinson's disease. We report that intranigral grafts promoted better survival of dopaminergic neurons and that only intranigral grafts induced recovery of fine motor skills and normalized cortico-striatal responses. The increase in the number of toxic activated glial cells in host tissue surrounding the intrastriatal graft, as well as within the graft, may be one of the causes of the increased cell death observed in the intrastriatal graft. Homotopic localization of the graft and the subsequent physiological cell rewiring of the basal ganglia may be a key factor in successful and beneficial cell transplantation procedures.
纹状体内胚胎腹侧中脑移植物已被证明在临床环境和帕金森病动物模型中能够整合、存活和重新支配宿主纹状体。然而，这种异位位置并不能恢复黑质纹状体通路的生理环路，只能促进适度的行为益处。在这里，我们在帕金森病动物模型中对纹状体内与纹状体外移植物的潜在益处进行了直接比较。我们报告说，纹状体内移植物促进了多巴胺能神经元更好的存活，只有纹状体内移植物诱导了精细运动技能的恢复和皮质纹状体反应的正常化。在纹状体内移植物周围的宿主组织以及移植物内，毒性激活的神经胶质细胞数量的增加，可能是观察到纹状体内移植物中细胞死亡增加的原因之一。移植物的同源定位和随后基底神经节的生理细胞重布线可能是成功和有益的细胞移植程序的关键因素。
