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Chunk #26 — RESULTS — iPSC-Derived Dopaminergic Neurons Survived and Ameliorate Behavioral Deficits in 6-OHDA PD Rats

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Efficient generation of functional dopaminergic neurons from human induced pluripotent stem cells under defined conditions.
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To investigate whether dopaminergic neurons derived from iPSCs exhibited functional properties, we transplanted the MR31-derived cells (20 days after the NSC stage) into 6-OHDA rats and conducted behavioral and histological studies, which we viewed as minimal criteria for assessing dopaminergic neuronal function. We first examined the behavior of sham-operated rats and rats received iPSC-derived dopaminergic neurons. As seen in Figure 3A, control rats that were transplanted with medium showed no attenuation of amphetamine-induced rotary behavior over the course of the experiment (12 weeks), whereas rats that were transplanted with grafts demonstrated significant rotational improvement at 12 weeks after transplantation (p < .05). Histological analysis revealed that donor cells (human antigen-immunopositive cells) coexpressing TH were found in all brains throughout the graft sites at 12 weeks (end of experiment) following the transplantation (Fig. 3B–3E). Cell counts in serial sections from one representative animal showed that the graft contained approximately 2,106 ± 313 TH-positive cells/mm3 human antigen-positive cells (donor-derived cells). This number of donor-derived dopaminergic neurons survived in the grafts was comparable with transplants with hESC-derived dopaminergic neurons [5]. We did not