A clonal line of mesencephalic progenitor cells converted to dopamine neurons by hematopoietic cytokines: A source of cells for transplantation in Parkinson's disease
A clonal line of mesencephalic progenitor cells converted to dopamine neurons by hematopoietic cytokines: A source of cells for transplantation in Parkinson's disease
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DOI：
10.1006/exnr.2001.7735
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发表时间：
2001-09-01
影响因子：
5.3
通讯作者：
Collier, TJ
中科院分区：
文献类型：
--
作者：
Carvey, PM;Ling, ZD;Collier, TJ
神经祖细胞可能提供无限的，按需的细胞来源移植到帕金森氏病（PD）患者，如果控制它们转化为多巴胺（DA）神经元所需的信号可以确定。我们最近发现，在造血系统中指导细胞分裂和分化的细胞因子可能在中枢神经系统中提供类似的功能。我们已经表明，有丝分裂祖细胞可以从胚胎大鼠中脑分离，这些细胞响应白细胞介素-1，白细胞介素-11，白血病抑制因子和神经胶质细胞系衍生的神经营养因子的组合产生酪氨酸羟化酶免疫反应（THir）表型的总细胞的20-25%。在本研究中，24个克隆细胞系来源于单细胞的中脑增殖球进行了检查，他们的反应的细胞因子混合物。选择产生最高百分比的THir神经元（98%）的克隆用于进一步研究。该克隆表达DA神经元的几种表型特征和Nurrl的表达。对细胞因子的反应在几代和冷冻保存几个月后是稳定的。当移植到纹状体的DA-耗尽大鼠，这些细胞衰减旋转不对称的程度相同，新鲜收获的胚胎DA神经元。这些数据表明，中脑祖细胞可以在培养中克隆扩增，并在造血细胞因子的存在下分化，以产生富集的DA神经元群体。当移植时，这些细胞在PD大鼠模型中提供显著的功能益处。(C)北京：科学出版社.
Neural progenitor cells potentially provide a limitless, on-demand source of cells for grafting into patients with Parkinson's disease (PD) if the signals needed to control their conversion into dopamine (DA) neurons could be identified. We have recently shown that cytokines which instruct cell division and differentiation within the hematopoeitic system may provide similar functions in the central nervous system. We have shown that mitotic progenitor cells can be isolated from embryonic rat mesencephalon and that these cells respond to a combination of interleukin-1, interleukin-11, leukemia inhibitory factor, and glial cell line-derived neurotrophic factor yielding a tyrosine hydroxylase-immunoreactive (THir) phenotype in 20-25% of total cells. In the present study, 24 clonal cell lines derived from single cells of mesencephalic proliferation spheres were examined for their response to the cytokine mixture. The clone yielding the highest percentage of THir neurons (98%) was selected for further study. This clone expressed several phenotypic characteristics of DA neurons and expression of Nurrl. The response to cytokines was stable for several passages and after cryopreservation for several months. When grafted into the striatum of DA-depleted rats, these cells attenuated rotational asymmetry to the same extent as freshly harvested embryonic DA neurons. These data demonstrate that mesencephalic progenitor cells can be clonally expanded in culture and differentiated in the presence of hematopoietic cytokines to yield enriched populations of DA neurons. When transplanted, these cells provide significant functional benefit in the rat model of PD. (C) 2001 Academic Press.