Human ESC-derived dopamine neurons show similar preclinical efficacy and potency to fetal neurons when grafted in a rat model of Parkinson's disease.
Bottom Line: Considerable progress has been made in generating fully functional and transplantable dopamine neurons from human embryonic stem cells (hESCs).We show long-term survival and functionality using clinically relevant MRI and PET imaging techniques and demonstrate efficacy in restoration of motor function with a potency comparable to that seen with human fetal dopamine neurons.Furthermore, we show that hESC-derived dopamine neurons can project sufficiently long distances for use in humans, fully regenerate midbrain-to-forebrain projections, and innervate correct target structures.
Affiliation: Developmental and Regenerative Neurobiology, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, 22184 Lund, Sweden; Lund Stem Cell Center, Lund University, 22184 Lund, Sweden. Electronic address: email@example.com.Show MeSH
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Mentions: Six months posttransplantation we observed robust survival in all hESC grafted animals (n = 8/8), with no signs of overgrowth or necrosis, similar in morphology to the intrastriatal grafts of hESC-DA neurons described above (Figures 1, 2D, and S2A–S2C). As observed with intranigral transplants of fetal VM, large numbers of hNCAM+ fibers projected rostral along the MFB and the adjacent nigrostriatal pathway (Figures 5A, 5F, S4A, and S4B). The axons extending along the MFB continued a distance more than 10 mm from the graft core and gave rise to dense terminal networks in amygdala (Figure 5B); dorsolateral striatum (Figure 5C) and piriform cortex; ventral striatum, including NAc (Figure 5D); olfactory tubercle; lateral septum; and large parts of the frontal lobe (Figures 5A, 5E, and 5G). hNCAM+ cells with a glial morphology were not detected in any of the hESC-grafted rats, consistent with our hypothesis that they are not essential for extensive axonal outgrowth.
Affiliation: Developmental and Regenerative Neurobiology, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, 22184 Lund, Sweden; Lund Stem Cell Center, Lund University, 22184 Lund, Sweden. Electronic address: firstname.lastname@example.org.