Distinctions between fetal and adult human platelet-derived growth factor-responsive neural precursors
Distinctions between fetal and adult human platelet-derived growth factor-responsive neural precursors
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DOI：
10.1002/ana.21421
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发表时间：
2008-08-01
影响因子：
11.2
通讯作者：
Weiss, Samuel
中科院分区：
文献类型：
--
作者：
Chojnacki, Andrew;Kelly, John J. P.;Weiss, Samuel
目的：血小板源性生长因子（PDGF）反应性神经前体细胞（PRP；也称为少突胶质细胞祖细胞）是啮齿动物中枢神经系统中特征最明确的前体细胞群之一。然而，由于明显无法大量培养和扩增人类 PRP，人们对人类 PRP 的生物学知之甚少。本研究旨在建立一种方法，可以直接比较胎儿和成人 PRP 的生物学特性，作为解决内在髓磷脂生成能力的潜在差异的方法。方法：我们在低铺板密度下使用神经球培养系统来分离、培养和比较胎儿和成人 PRP 的特性。结果：PDGF 刺激胎儿 PRP 生成主要分化为少突胶质细胞的神经球，少突胶质细胞获得髓磷脂碱性蛋白表达，以及神经元和神经元。少量星形胶质细胞。成纤维细胞生长因子 2 与 PDGF 一起促进胎儿人 PRP 扩增。相比之下，从胼胝体中分离出的成人 PRP 需要两倍的培养时间才能产生神经球，其中含有少突胶质细胞和星形胶质细胞，但不含有神经元。引人注目的是，成纤维细胞生长因子 2 也不促进成人 PRP 自我更新。解释：胎儿和成人 PRP 内在增殖、表型和自我更新特性的差异表明它们是不同的群体，这可能导致不同的髓磷脂生成能力。
Objective: Platelet-derived growth factor (PDGF)-responsive neural precursors (PRPs; also known as oligodendrocyte progenitor cells) are one of the best characterized precursor cell populations of the rodent central nervous System. Yet little is known about the biology of human PRPs because of an apparent inability to culture and expand them in large numbers. This Study was designed to establish an approach that allows direct comparisons between the biology of fetal and adult human PRPs, as a means to address potential differences in intrinsic myelin-production capabilities.Methods: We used the neurosphere culture system, under low plating density, to isolate, culture, and compare the properties of fetal and adult human PRPs.Results: PDGF stimulated fetal human PRPs to generate neurospheres that differentiated primarily into oligodendrocytes, which acquired myelin basic protein expression, as well as neurons and a small number of astrocytes. Together with PDGF, fibroblast growth factor 2 promoted fetal human PRP expansion. In contrast, adult human PRPs isolated from the corpus callosum required twice the culture period to generate neurospheres, which contained oligodendrocytes, as well as astrocytes, but not neurons. Strikingly, fibroblast growth factor 2 did nor promote adult human PRP self-renewal.Interpretation: Differences in the intrinsic proliferation, phenotype, and self-renewal properties of fetal and adult human PRPs Suggest they are distinct populations, which may result in distinct myelin-production capabilities.