Fig. 5: RA-specified vMB preparations differentiate into functional dopaminergic neurons and restore motor deficits after transplantation into a rat model of PD.

a–m Immunohistological analysis of unilaterally 6-OHDA lesioned rats seven months after grafting of vMB preparations into the striatum. a Overview of graft-derived innervation to the host brain labeled with DAB-developed hNCAM staining, and magnification of human neuronal fiber outgrowth toward prefrontal cortex (PFC) and dorsolateral striatum (DLstr). b TH expression in striatum and substantia nigra (SN). Note TH immuno-reactivity throughout the striatum and lack of TH expression in the SN on the lesioned side (right). c–m Immunohistochemistry of indicated markers in grafts. n Quantification of the percentage of TH⁺ cells in grafts expressing EN1, SOX6, GIRK2 (n = 6 rats), PITX3 or CALB1 (n = 4 rats). Data presented as mean ± S.D. o Quantification of net rotations per minute in rats with baseline amphetamine-induced rotation scores ≥5 ipsilateral turns per minute (n = 5 rats) after lesion and seven months after transplantation. Data presented as mean ± S.E.M, p value from Welch’s unequal variance two-tailed t-test. p Rotational behavior over time after administration of amphetamine before (solid lines) and seven months after (dashed lines) grafting of all grafted animals (n = 9 rats). q Preference for contralateral paw use after lesion and seven months after transplantation. Data presented as mean±S.E.M (n = 9 rats). o–q the same rats analyzed post-lesion were analyzed seven months post-transplantation. Scale bars: 1000 µm in (a). left and (b), 100 µm in (a). right; 25 µm in (d, e, f, I, j, k); 10 µm in (c, g, h, l, m).