Noggin Enhances Dopamine Neuron Production from Human Embryonic Stem Cells and Improves Behavioral Outcome After Transplantation into Parkinsonian Rats
Noggin Enhances Dopamine Neuron Production from Human Embryonic Stem Cells and Improves Behavioral Outcome After Transplantation into Parkinsonian Rats
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DOI：
10.1634/stemcells.2008-0085
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发表时间：
2008-01-01
期刊：
影响因子：
5.2
通讯作者：
Freed, Curt R.
中科院分区：
文献类型：
--
作者：
Chiba, Shunmei;Lee, Young Mook;Freed, Curt R.
通过移植从流产的胎儿组织中恢复的胎儿多巴胺神经元，帕金森病的症状已经得到改善，但组织恢复是困难的。如果人类胚胎干细胞能够转化为多巴胺神经元并移植到大脑中，可能会为移植提供无限的细胞。我们发现，骨形态发生蛋白拮抗剂Noggin增加了体外分化的人和小鼠胚胎干细胞在小鼠PA6基质细胞上产生的多巴胺神经元的数量。无论是早期(对于小鼠，0-7天，对于人类，0-9天)或持续治疗，都可以看到诺金效应。在移植到环孢素免疫抑制的大鼠体内后，人多巴胺神经元改善了阿朴吗啡循环，这与存活的多巴胺神经元的数量直接相关，在诺金治疗后，阿朴吗啡循环的数量是仅在PA6细胞上分化的对照人类胚胎干细胞移植的五倍。我们得出结论，Noggin促进人和小鼠胚胎干细胞的多巴胺神经元分化和存活。干细胞2008；26：2810-2820
Symptoms of Parkinson's disease have been improved by transplantation of fetal dopamine neurons recovered from aborted fetal tissue, but tissue recovery is difficult. Human embryonic stem cells may provide unlimited cells for transplantation if they can be converted to dopamine neurons and survive transplantation into brain. We have found that the bone morphogenic protein antagonist Noggin increased the number of dopamine neurons generated in vitro from human and mouse embryonic stem cells differentiated on mouse PA6 stromal cells. Noggin effects were seen with either early (for mouse, days 0-7, and for human, days 0-9) or continuous treatment. After transplant into cyclosporin-immunosuppressed rats, human dopamine neurons improved apomorphine circling in direct relation to the number of surviving dopamine neurons, which was fivefold greater after Noggin treatment than with control human embryonic stem cell transplants differentiated only on PA6 cells. We conclude that Noggin promotes dopamine neuron differentiation and survival from human and mouse embryonic stem cells. STEM CELLS 2008;26:2810-2820