Yin Tong, Li Linheng
Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA.
J Clin Invest. 2006 May;116(5):1195-201. doi: 10.1172/JCI28568.
The stem cell niche is composed of a specialized population of cells that plays an essential role in regulating adult stem cell self-renewal and differentiation. In adults, osteoblasts, responsible for osteogenesis, and hematopoietic cells, responsible for hematopoiesis, are closely associated in the bone marrow, suggesting a reciprocal relationship between the two. It was recently discovered that a subset of osteoblasts functions as a key component of the HSC niche (namely, the osteoblastic niche), controlling HSC numbers. HSCs interact not only with osteoblasts but also with other stromal cells, including endothelial cells. Sinusoidal endothelial cells in bone marrow have been revealed as an alternative HSC niche called the vascular niche. In this Review we compare the architecture of these 2 HSC niches in bone marrow. We also highlight the function of osteoblasts in maintaining a quiescent HSC microenvironment and the likely role of the vascular niche in regulating stem cell proliferation, differentiation, and mobilization. In addition, we focus on studies of animal models and in vitro assays that have provided direct insights into the actions of these osteoblastic and vascular niches, revealing central roles for numerous signaling and adhesion molecules. Many of the discoveries described herein may contribute to future clinical treatments for hematopoietic and bone-related disorders, including cancer.
干细胞生态位由一群特殊的细胞组成,这些细胞在调节成体干细胞自我更新和分化中发挥着至关重要的作用。在成体中,负责骨生成的成骨细胞和负责造血的造血细胞在骨髓中紧密相连,这表明两者之间存在相互关系。最近发现,一部分成骨细胞作为造血干细胞生态位(即成骨细胞生态位)的关键组成部分,控制着造血干细胞的数量。造血干细胞不仅与成骨细胞相互作用,还与包括内皮细胞在内的其他基质细胞相互作用。骨髓中的窦状内皮细胞已被揭示为一种名为血管生态位的替代造血干细胞生态位。在本综述中,我们比较了骨髓中这两种造血干细胞生态位的结构。我们还强调了成骨细胞在维持静止造血干细胞微环境中的作用以及血管生态位在调节干细胞增殖、分化和动员方面可能发挥的作用。此外,我们重点关注动物模型和体外试验的研究,这些研究为这些成骨细胞和血管生态位的作用提供了直接见解,揭示了众多信号分子和黏附分子的核心作用。本文所述的许多发现可能有助于未来针对造血和骨骼相关疾病(包括癌症)的临床治疗。