Tissue-specific muscle, neural and liver stem/progenitor cells reside in the bone marrow, respond to an SDF-1 gradient and are mobilized into peripheral blood during stress and tissue injury
Tissue-specific muscle, neural and liver stem/progenitor cells reside in the bone marrow, respond to an SDF-1 gradient and are mobilized into peripheral blood during stress and tissue injury
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DOI：
10.1016/j.bcmd.2003.09.025
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发表时间：
2004-01-01
影响因子：
2.3
通讯作者：
Ratajczak, MZ
中科院分区：
文献类型：
--
作者：
Kucia, M;Ratajczak, J;Ratajczak, MZ
一些报道暗示骨髓造血干细胞转分化为组织特异性干细胞;然而，尚未充分处理骨髓中预先存在的定向组织特异性干细胞的可能性。我们在这里提出了一个替代的解释所谓的干细胞转分化现象。首先，我们假设组织定向干/祖细胞在外周血中循环并竞争组织特异性小生境。这些细胞的循环在维持身体远端部位的干细胞库中起着重要的生理作用，并且可以通过施用与用于动员造血干细胞的那些类似的试剂来增加外周血中这些细胞的数量。其次，我们假设骨髓组织是各种干细胞趋化因子和生存因子的来源，并提供了一个环境，趋化组织特异性循环干/祖细胞。在这种情况下，我们设想骨髓不仅是造血干细胞的“家”或“藏身之地”，而且是已经分化的循环组织特异性干细胞/祖细胞的“家”或“藏身之地”。为了支持这一概念，我们在这里报告说，肌肉（Myf-5、Myo-D）、神经（GFAP、巢蛋白）和肝脏（CK 19、胎蛋白）的几种早期标志物的mRNA在循环（贴壁细胞耗尽）外周血单核细胞中可检测到。此外，使用实时RT-PCR，我们发现这些标记物的表达水平增加后，动员G-CSF的人和小鼠的外周血。此外，使用基质衍生因子-1（SDF-1）趋化性和实时RT-PCR分析，我们提出的证据表明，早期组织特异性干细胞存在于正常的人类和小鼠骨髓中，在其表面表达CXCR4受体，并可以高度富集（在人类和小鼠）趋化后，SDF-1梯度。我们所有的实验都是在新鲜分离的细胞上进行的，以排除培养物中转分化的造血干细胞或间充质细胞的潜在贡献。我们认为任何使用骨髓细胞群的转分化研究都应该排除表面上纯的造血干细胞群实际上可能含有预先存在的组织特异性干/祖细胞的可能性。(C)2003年爱思唯尔公司All rights reserved.
Several reports imply that bone marrow hematopoietic stem cells transdifferentiate into tissue-specific stem cells; however, the possibility of committed tissue-specific stem cells pre-existing in the bone marrow has not been dealt with adequately. We present here an alternative explanation of the so-called phenomenon of stem cell transdifferentiation. First, we postulate that tissue-committed stem/progenitor cells circulate in the peripheral blood and compete for tissue-specific niches. The circulation of these cells plays an important physiological role in maintaining a pool of stem cells in distant parts of the body and the number of these cells in peripheral blood can be increased by the administration of agents similar to those used for mobilization of hematopoietic stem cells. Second, we postulate that bone marrow tissue is a source of various stem-cell chemoattractants and survival factors and provides an environment that chemoattracts tissue-specific circulating stem/progenitor cells. In this context, we envision bone marrow as a "home" or "hide-out place" not only of hematopoietic stem cells but also of already differentiated circulating tissue-specific stem/progenitors. In support of this concept, we report here that mRNA of several early markers for muscle (Myf-5, Myo-D), neural (GFAP, nestin) and liver (CK19, fetoprotein) is detectable in circulating (adherent cell-depleted) peripheral blood mononuclear cells. Moreover, using real-time RT-PCR, we found that the level of expression of these markers increases in the peripheral blood of humans and mice after mobilization by G-CSF. Furthermore, using stromal-derived factor-1 (SDF-1) chemotaxis and realtime RT-PCR analysis, we present evidence that early tissue-specific stem cells reside in normal human and murine bone marrow, express the CXCR4 receptor on their surface and can be highly enriched (in humans and mice) after chemotaxis to SDF-1 gradient. All our experiments were performed on freshly isolated cells to exclude the potential contribution of transdifferentiated hematopoietic stem or mesenchymal cells in the culture. We maintain that any transdifferentiation studies employing populations of bone marrow cells should rule out the possibility that the apparently pure hematopoietic stem cell population could in fact contain pre-existing tissue-specific stem/progenitors. (C) 2003 Elsevier Inc. All rights reserved.