Neural Stem Cells Derived from Human Parthenogenetic Stem Cells Engraft and Promote Recovery in a Nonhuman Primate Model of Parkinson's Disease

作者：Rodolfo Gonzalez, Ibon Garitaonandia, Maxim Poustovoitov, Tatiana Abramihina, Caleb R.S. McEntire, Ben Culp, Jordan Attwood, Alexander Noskov, Trudy Christiansen-Weber, Marwa Khater, Sergio Mora-Castilla, Cuong To, Andrew Crain, Glenn Sherman, Andrey Semechkin, Louise Chang Laurent, John D. Elsworth, John R. Sladek, Evan Y. Snyder, D. Eugene Redmond, Russell Kern · 发表于：Cell Transplantation · 年份：2016 · DOI：10.3727/096368916x691682 · 被引用次数：75 · 研究领域：Pluripotent Stem Cells Research、Neurological disorders and treatments、Nuclear Receptors and Signaling

Cell therapy has attracted considerable interest as a promising therapeutic alternative for patients with Parkinson's disease (PD). Clinical studies have shown that grafted fetal neural tissue can achieve considerable biochemical and clinical improvements in PD. However, the source of fetal tissue grafts is limited and ethically controversial. Human parthenogenetic stem cells offer a good alternative because they are derived from unfertilized oocytes without destroying potentially viable human embryos and can be used to generate an unlimited supply of neural cells for transplantation. We have previously reported that human parthenogenetic stem cell-derived neural stem cells (hpNSCs) successfully engraft, survive long term, and increase brain dopamine (DA) levels in rodent and nonhuman primate models of PD. Here we report the results of a 12-month transplantation study of hpNSCs in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned African green monkeys with moderate to severe clinical parkinsonian symptoms. The hpNSCs manufactured under current good manufacturing practice (cGMP) conditions were injected bilaterally into the striatum and substantia nigra of immunosuppressed monkeys. Transplantation of hpNSCs was safe and well tolerated by the animals with no dyskinesia, tumors, ectopic tissue formation, or other test article-related serious adverse events. We observed that hpNSCs promoted behavioral recovery; increased striatal DA concentration, fiber innervation, an...