Human embryonic stem cell-derived neural precursors develop into neurons and integrate into the host brain.
Whether and how in-vitro-produced human neural precursors mature and integrate into the brain are crucial to the utility of human embryonic stem (hES) cells in treating neurological disorders. After transplantation into the ventricles of neonatal immune-deficient mice, hES-cell-derived neural precursors stopped expressing the cell division marker Ki67, except in neurogenic areas, and differentiated into neurons and then glia in a temporal course intrinsic to that of human cells regardless of location. The human cells located in the gray matter became neurons in the olfactory bulb and striatum, whereas those in the white matter produced exclusively glia. Importantly, the grafted human cells formed synapses. Thus, the in-vitro-produced human neural precursors follow their intrinsic temporal program to produce neurons and glia and, in response to environmental signals, generate cells appropriate to their target regions and integrate into the brain.
Guillaume
Daniel J
DJ
Departments of Anatomy and Neurology, School of Medicine, The Waisman Center, University of Wisconsin, Madison, Wisconsin 53705, USA.
Johnson
M Austin
MA
Li
Xue-Jun
XJ
Zhang
Su-Chun
SC
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology* / Q000196:embryology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002490:Central Nervous System / Q000166:cytology / Q000254:growth & development; D053595:Embryonic Stem Cells / Q000502:physiology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D019394:Ki-67 Antigen; D051379:Mice; D016513:Mice, SCID; D008854:Microscopy, Electron; D046569:Neuroepithelial Cells / Q000637:transplantation; D009474:Neurons / Q000502:physiology*; D033581:Stem Cell Transplantation; D013569:Synapses / Q000502:physiology
D019394:Ki-67 Antigen