Figure 1.

Functional Imaging of Long-Term Surviving Intrastriatal Transplants of hESC-DA Neurons

(A) MRI and PET scans for ¹⁸F-fallypride, ¹⁸F-LBT999 after 6-OHDA lesion, show an increase in binding of ¹⁸F-fallypride (n = 6) on the side of lesion indicating an impaired DA release, confirmed by a loss of ¹⁸F-LBT999 (n = 7) binding due to loss of DAT binding sites. At 5 months posttransplantation both ¹⁸F-fallypride (n = 11) and ¹⁸F-LBT999 (n = 14) binding are restored toward normal, indicative of a graft rich in functional DA neurons, in the absence of any detectable microglial response, as assessed with ¹⁸F-DPA714 (n = 13).

(B) Quantitative measurements of binding ratios between intact and lesioned striatum revealed an increased binding potential of ¹⁸F-fallypride in the 6-OHDA denervated striatum, which was normalized to intact levels 5 months posttransplantation of hESC-DA neurons.

(C) A 6-OHDA lesion resulted in a near complete loss of ¹⁸F-LBT999 binding due to the loss of DAT-expressing dopaminergic terminals, which was restored toward normal posttransplantation.

(D and E) Immunohistochemistry of hNCAM revealed neuron-rich grafts of hESC-DA neurons 6 months posttransplantation, providing extensive innervation of the host CPu and surrounding extrastriatal dopaminergic targets, such as NAc.

(F and G) Away from the graft core, widespread innervation by human axons was found in known DA target structures within the prefrontal cortex.

See also Figure S1. AC, anterior commissure; CPu, caudate-putamen unit; FM, forceps minor; NAc, nucleus accumbens; PrL, prelimbic cortex; T, transplant. In (B) and (C), data are represented as mean ± SEM. ^∗p < 0.01. In (A), (D), and (F), scale bars represent 1 mm. In (E) and (G), scale bars represent 0.5 mm.