In vitro differentiation of transplantable neural precursors from human embryonic stem cells.
The remarkable developmental potential and replicative capacity of human embryonic stem (ES) cells promise an almost unlimited supply of specific cell types for transplantation therapies. Here we describe the in vitro differentiation, enrichment, and transplantation of neural precursor cells from human ES cells. Upon aggregation to embryoid bodies, differentiating ES cells formed large numbers of neural tube-like structures in the presence of fibroblast growth factor 2 (FGF-2). Neural precursors within these formations were isolated by selective enzymatic digestion and further purified on the basis of differential adhesion. Following withdrawal of FGF-2, they differentiated into neurons, astrocytes, and oligodendrocytes. After transplantation into the neonatal mouse brain, human ES cell-derived neural precursors were incorporated into a variety of brain regions, where they differentiated into both neurons and astrocytes. No teratoma formation was observed in the transplant recipients. These results depict human ES cells as a source of transplantable neural precursors for possible nervous system repair.
Zhang
S C
SC
Department of Anatomy, University of Wisconsin 1500 Highland Avenue, Madison, WI 53705, USA. zhang@waisman.wisc.edu
Wernig
M
M
Duncan
I D
ID
Brüstle
O
O
Thomson
J A
JA
D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D019070:Cell Lineage; D017690:Cell Transplantation; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology; D004622:Embryo, Mammalian / Q000166:cytology*; D004847:Epithelial Cells / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D009474:Neurons / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*
D016222:Fibroblast Growth Factor 2; D001973:Bromodeoxyuridine