Morshead Cindi M, Benveniste Patricia, Iscove Norman N, van der Kooy Derek
Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
Nat Med. 2002 Mar;8(3):268-73. doi: 10.1038/nm0302-268.
The concept of stem-cell plasticity received strong support from a recent observation that extensively passaged, clonally derived neural stem cells could contribute to hematopoiesis. We investigated whether hematopoietic potential was a consistent or unusual feature of neural stem cells, and whether it depended on the extent of in vitro passaging before transplantation. Here we transplanted over 128 x 10(6) neurosphere cells into 128 host animals; however, we never observed contribution to hematopoiesis, irrespective of the number of passages and despite the use of an assay that could detect the contribution of a single blood stem cell to hematopoietic repopulation. Although extensively cultured neurosphere cells continued to generate neural progeny, marked changes in their growth properties occurred, including changes in growth-factor dependence, cell-cycle kinetics, cell adhesion and gene expression. Our results exclude hematopoietic competence as a consistent property of intravenously infused neural stem cells. However, the consistent changes that occurred during extended passaging are compatible with genetic or epigenetic alterations and suggest that rare transformation events may account for the neural-to-blood fate switch originally reported.
干细胞可塑性的概念得到了最近一项观察结果的有力支持，即经过大量传代培养的克隆来源神经干细胞能够参与造血过程。我们研究了造血潜能是神经干细胞的一种普遍特征还是罕见特征，以及它是否取决于移植前体外传代的程度。在此，我们将超过128×10⁶个神经球细胞移植到128只宿主动物体内；然而，无论传代数多少，且尽管使用了能够检测单个血液干细胞对造血重建贡献的检测方法，我们从未观察到对造血过程的参与。虽然经过大量培养的神经球细胞继续产生神经后代，但其生长特性发生了显著变化，包括对生长因子依赖性、细胞周期动力学、细胞黏附及基因表达的变化。我们的结果排除了造血能力是静脉输注神经干细胞的普遍特性这一可能性。然而，长时间传代过程中发生的持续变化与基因或表观遗传改变相符，并表明罕见的转化事件可能是最初报道的神经向血液命运转变的原因。
