Fig. 7.

Host-to-graft transmission of α-syn pathology prevented by cografted astrocytes. (A) Schematic summary of the experimental procedure. α-synucleinopathic striatal environments were built by bilateral injection of the α-syn AAV2+PFF into the rat striatum. One month later, the dopamine neurogenic NSCs were transplanted into the left side of the α-synucleinopathic striatum, while the mixture of the NSCs with VM astrocytes, Ctx astrocytes, or ACSA-2-MACS–isolated astrocytes (2:1) was transplanted into the right striatum. (B–E) Effect of VM-astrocyte cografting on host-to-graft α-syn transmission and DA neuron engraftment. Representative images for pS129-αsyn+/TH+ grafts in the left and right striatum from two different rats (B and C). The boxed areas were enlarged in the neighboring images. pS129-αsyn expression in graft, estimated by MFI using LAS image analysis (Leica) (D). TH+ cells in graft (E). Significant differences from the left side of the striatum of identical animals at ^###P < 0.001, n = 8 rats, paired t test. (Scale bars: 500 μm in B, 100 μm in C.) (F and G) Comparison of cografting effects of astrocytes from different origins. Host-to-graft α-syn propagation and DA neuron engraftment were assessed by the intensity of pS129-α-syn immunoreactivity (F) and the number of TH+ cells (G) in the grafts. Significant differences from the VM astrocyte cografted at ^###P < 0.001 and between the groups indicated at ***P < 0.001, n = 8 (VM-Ast), 4 (Ctx-Ast), and 4 (MACS-sorted Ast); one-way ANOVA.