Therapeutic targeting of a stem cell niche
Therapeutic targeting of a stem cell niche
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DOI：
10.1038/nbt1281
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发表时间：
2007-02-01
影响因子：
46.9
通讯作者：
Scadden, David T.
中科院分区：
文献类型：
--
作者：
Adams, Gregor B.;Martin, Roderick P.;Scadden, David T.
干细胞所处的专门微环境或利基环境提供了调节干细胞功能的输入。我们使用与造血干细胞临床应用相关的三个小鼠模型，验证了以利基为目标的假设可能会改善基于干细胞的治疗。我们和其他人之前确认成骨细胞是成年HS细胞生态位的组成部分，并证实成骨细胞上甲状旁腺激素(PTH)受体的激活会增加干细胞数量(1-3个)。在这里，我们展示了甲状旁腺素的药理学应用增加了动员到外周血中用于干细胞采集的HS细胞的数量，保护干细胞免受细胞毒性化疗的反复暴露，并在移植受者中扩大干细胞。这些数据提供了证据，表明这个利基可能是基于药物的干细胞疗法的一个有吸引力的目标。
The specialized microenvironment or niche where stem cells reside provides regulatory input governing stem cell function. We tested the hypothesis that targeting the niche might improve stem cell-based therapies using three mouse models that are relevant to clinical uses of hematopoietic stem ( HS) cells. We and others previously identified the osteoblast as a component of the adult HS cell niche and established that activation of the parathyroid hormone ( PTH) receptor on osteoblasts increases stem cell number(1-3). Here we show that pharmacologic use of PTH increases the number of HS cells mobilized into the peripheral blood for stem cell harvests, protects stem cells from repeated exposure to cytotoxic chemotherapy and expands stem cells in transplant recipients. These data provide evidence that the niche may be an attractive target for drug-based stem cell therapeutics.