Although mouse and human iPSCs have been used to generate (DA) neurons that were beneficial in rat models of PD, human iPSC-derived neural progenitor cells (NPCs) have not been examined in primate brains.
Investigators at Kyoto University (Japan) generated NPCs at different stages of predifferentiation using a feeder-free culture method, and grafted them into the brains of a monkey PD model and NOD-SCID mice.
They reported in the December 29, 2011, online edition of the Journal of Parkinson's Disease that magnetic resonance imaging (MRI), positron emission tomography (PET), immunocytochemistry, and behavioral analyses revealed that NPCs pretreated with Sonic hedgehog and fibroblast growth factor-8 followed by glial cell–derived neurotrophic factor, brain-derived neurotrophic factor, ascorbic acid, and dibutyryl cyclic AMP resulted in smaller grafts than those without these treatments, and survived as DA neurons in a monkey brain as long as six months.
“In previous studies, midbrain DA neurons were induced from human iPSCs, but the method required coculture with stromal mouse feeder cells or Matrigel,” said senior author Dr. Jun Takahashi, professor of neurosurgery at Kyoto University. "Our feeder-free method would be more suitable for clinical use. We developed a series of methods to induce human iPSCs to become NPCs, using a feeder-free culture method, and grafted NPCs at different stages of differentiation into the brain of a monkey PD model. We developed a method to evaluate the growth and DA activity of the grafts using MRI, PET, immunocytochemistry, and behavioral analyses, all of which will be useful in preclinical research.”
“Our results contribute to the evaluation of the survival, differentiation, and function of human iPSC-derived neuronal cells in a primate PD model,” said Dr. Takahashi. “Although we have to perform additional preclinical studies using more primate models before clinical application, we believe our findings contribute as the first step for developing a strategy for cell replacement therapy in Parkinson's disease.”
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