Generation of Regionally Specified Neural Progenitors and Functional Neurons from Human Embryonic Stem Cells under Defined Conditions

被引：520

作者：

Kirkeby, Agnete ^{[1
,2
]}

Grealish, Shane ^{[1
]}

Wolf, Daniel A. ^{[1
,2
]}

Nelander, Jenny ^{[1
,2
]}

Wood, James ^{[2
,3
]}

Lundblad, Martin ^{[1
]}

Lindvall, Olle ^{[2
,3
]}

Parmar, Malin ^{[1
,2
]}

机构：

[1] Lund Univ, Dept Expt Med Sci, SE-22184 Lund, Sweden

[2] Lund Univ, Lund Stem Cell Ctr, SE-22184 Lund, Sweden

[3] Lund Univ, Dept Clin Sci, SE-22184 Lund, Sweden

来源：

CELL REPORTS | 2012年 / 1卷 / 06期

基金：

瑞典研究理事会;

关键词：

MIDBRAIN DOPAMINE NEURONS; PARKINSONS-DISEASE; HUMAN ES; FLOOR PLATE; RAT MODEL; IN-VITRO; VENTRAL MESENCEPHALON; SUBSTANTIA-NIGRA; IPS CELLS; LINES;

D O I：

10.1016/j.celrep.2012.04.009

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

To model human neural-cell-fate specification and to provide cells for regenerative therapies, we have developed a method to generate human neural progenitors and neurons from human embryonic stem cells, which recapitulates human fetal brain development. Through the addition of a small molecule that activates canonical WNT signaling, we induced rapid and efficient dose-dependent specification of regionally defined neural progenitors ranging from telencephalic forebrain to posterior hindbrain fates. Ten days after initiation of differentiation, the progenitors could be transplanted to the adult rat striatum, where they formed neuron-rich and tumor-free grafts with maintained regional specification. Cells patterned toward a ventral midbrain (VM) identity generated a high proportion of authentic dopaminergic neurons after transplantation. The dopamine neurons showed morphology, projection pattern, and protein expression identical to that of human fetal VM cells grafted in parallel. VM-patterned but not forebrain-patterned neurons released dopamine and reversed motor deficits in an animal model of Parkinson's disease.

引用

页码：703 / 714

页数：12

共 46 条

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