title: Proof of concept studies exploring the safety and functional activity of human parthenogenetic-derived neural stem cells for the treatment of Parkinson's disease.
abstract: Recent studies indicate that human pluripotent stem cell (PSC)-based therapies hold great promise in 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 viable human embryos and can be used to generate an unlimited supply of neural stem cells for transplantation. Here we evaluate for the first time the safety and engraftment of human parthenogenetic stem cell-derived neural stem cells (hpNSCs) in two animal models: 6-hydroxydopamine (6-OHDA)-lesioned rodents and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated nonhuman primates (NHPs). In both rodents and nonhuman primates, we observed successful engraftment and higher dopamine levels in hpNSC-transplanted animals compared to vehicle control animals, without any adverse events. These results indicate that hpNSCs are safe, well tolerated, and could potentially be a source for cell-based therapies in PD.
authors.affiliation: International Stem Cell Corporation, Carlsbad, CA, USA.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Gonzalez
authors.forename: Ibon
authors.initials: I
authors.lastname: Garitaonandia
authors.forename: Andrew
authors.initials: A
authors.lastname: Crain
authors.forename: Maxim
authors.initials: M
authors.lastname: Poustovoitov
authors.forename: Tatiana
authors.initials: T
authors.lastname: Abramihina
authors.forename: Alexander
authors.initials: A
authors.lastname: Noskov
authors.forename: Chuan
authors.initials: C
authors.lastname: Jiang
authors.forename: Robert
authors.initials: R
authors.lastname: Morey
authors.forename: Louise C
authors.initials: LC
authors.lastname: Laurent
authors.forename: John D
authors.initials: JD
authors.lastname: Elsworth
authors.forename: Evan Y
authors.initials: EY
authors.lastname: Snyder
authors.forename: D Eugene
authors.initials: DE
authors.lastname: Redmond
authors.forename: Ruslan
authors.initials: R
authors.lastname: Semechkin
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002522:Chlorocebus aethiops; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004298:Dopamine / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020267:MPTP Poisoning / Q000628:therapy*; D008856:Microscopy, Fluorescence; D058953:Neural Stem Cells / Q000166:cytology / Q000637:transplantation*; D010063:Ovum / Q000166:cytology*; D016627:Oxidopamine / Q000633:toxicity; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D016627:Oxidopamine; D004298:Dopamine