Nature Biotechnology
16, 1033 - 1039 (1998)
doi:10.1038/3473
Engraftable human neural stem cells respond to development cues, replace
neurons, and express foreign genesJonathan D. Flax5, Sanjay Aurora5, Chunhua Yang, Clemence Simonin, Ann Marie Wills, Lori L. Billinghurst, Moncef Jendoubi1, Richard L. Sidman2, John H. Wolfe3, Seung U. Kim4
& Evan Y. Snyder
Departments of Neurology, Pediatrics, and Neurosurgery, Children's
Hospital, Harvard Medical School, Boston, MA. 1
National Eye Institute, National Institute of Health
, Bethesda, MD. 2
New England Regional Primate Center, Harvard Medical
School, Southborough, MA. 3
Department of Pathobiology and Center for Comparative
Medical Genetics, School of Veterinary Medicine, University of Pennsylvania
, Philadelphia, PA. 4
Division of Neurology, Department of Medicine, University
Hospital, University of British Columbia, Vancouver,
BC, Canada. 5
These authors contributed equally to this work.
Correspondence should be addressed to Evan Y. Snyder Corresponding author (Snyder@A1.TCH.Harvard.edu
).cell therapyprogenitor cellgene therapyTay-Sachs diseasetransplanationdifferentiationStable clones of neural stem cells (NSCs) have been isolated from the human
fetal telencephalon. These self-renewing clones give rise to all fundamental
neural lineages in vitro. Following transplantation into germinal zones of
the newborn mouse brain they participate in aspects of normal development,
including migration along established migratory pathways to disseminated central
nervous system regions, differentiation into multiple developmentally and
regionally appropriate cell types, and nondisruptive interspersion with host
progenitors and their progeny. These human NSCs can be genetically engineered
and are capable of expressing foreign transgenes in vivo. Supporting their
gene therapy potential, secretory products from NSCs can correct a prototypical
genetic metabolic defect in neurons and glia in vitro. The human NSCs can
also replace specific deficient neuronal populations. Cryopreservable human
NSCs may be propagated by both epigenetic and genetic means that are comparably
safe and effective. By analogy to rodent NSCs, these observations may allow
the development of NSC transplantation for a range of disorders.
|
