2-B-P-050 〇西村 周泰^1,2、儀間 芹菜²、扇田 隆司³、斎藤 博幸⁴、高田 和幸² Kaneyasu Nishimura^1,2, Serina Gima², Takashi Ohgita³, Hiroyuki Saito⁴, Kazuyuki Takata^{2 1}同志社大・院脳・脳回路機能創出、²京都薬科大・薬・シナジーラボ、³京都薬科大・薬・共同利用機器セ、⁴京都薬科大・薬・薬品物理化学 ¹Lab. Func. Brain Construct. Doshisha Univ., ²Joint Res. Lab., Kyoto Pharm. Univ., ³Cent. Instru. Anal., Kyoto Pharm. Univ., ⁴Dept. Biophys. Chem., Kyoto Pharm. Univ. Clinical trials of cell transplantation therapy using fetal mesencephalic tissue provided a proof-of-concept for regenerative therapy for the patients with Parkinson's disease. Postmortem studies of the patients who received fetal grafts revealed that α-synuclein (α-syn)⁺ Lewy body-like inclusions were emerged in long-term transplantation and may reduce the clinical outcomes even the grafts were well survived in the recipients. Various studies were conducted to reveal that the host derived α-syn are transferred to the grafted neurons to assess the exsert of α-syn⁺ inclusions in the grafts. However, these studies remain the possibility to detect the intrinsic expression of α-syn in the grafted neurons. Here, we demonstrated that the human α-syn preformed fibrils inoculated into the cerebral cortex were transferred to SNCA^-/- human induced pluripotent stem cell-derived midbrain dopaminergic (mDA) neurons grafted into the striatum of rats. Because grafted SNCA^-/- hiPSC-derived mDA neurons lack the intrinsic expression of α-syn protein, the human α-syn-immunoreactivity found in the grafted cells should be derived from the host brain. Our results clearly showed that host-to-graft propagation of α-syn was occurred, and this work contributes to understand the molecular mechanisms to form the α-syn inclusions in the grafted mDA neurons.