Wnt5a-treated midbrain neural stem cells improve dopamine cell replacement therapy in parkinsonian mice
J. Clin. Invest. Clare L. Parish, et al. 118:149 doi:10.1172/JCI32273 [Go to this article.]

Figure 4
Transplantation of Wnt5a-overexpressing VMNs induces behavioral and cellular recovery in parkinsonian mice. (A) Time course of amphetamine-induced rotational behavior in sham-, VMN-, and VMN-Wnt5a–grafted animals. VMN transplants resulted in significant behavioral improvement at 8 weeks, while VMN-Wnt5a transplants resulted in full restoration of behavior. (B) Confirmation of behavioral improvements following apomorphine-induced rotational testing at 8 weeks. (C) Number of TH⁺ cells within the striatum of grafted animals. (D–F) Photomicrographs in the striatum of grafts from sham-operated (D), VMN-grafted (E), and VMN-Wnt5a–grafted (F) mice. (G) High-power image of DA neurons residing within a VMN-Wnt5a graft showing classical bipolar morphology (arrow). (H) High-power image of a hypertrophied TH⁺ fiber located outside the graft site (arrowhead in F). (I) Area of TH-immunoreactive fibers within the striatum following grafting. (J) Area of fibers per TH cell. Note that regardless of the increase in cell numbers, the density of fibers per cell in VMN-Wnt5a grafts was significantly greater, suggesting neuritogenesis and greater integration into the host tissue. Data are mean ± SD (n = 6 per group). *P < 0.05; **P < 0.01; ***P < 0.001, ANOVA with Tukey post-hoc test. Scale bars: 200 μm (D–F); 50 μm (G); 100 μm (H).