Wilmot Cancer Center, Rochester, New York, USA.
Tissue Eng Part B Rev. 2011 Dec;17(6):415-22. doi: 10.1089/ten.TEB.2011.0197. Epub 2011 Sep 27.
Hematopoietic stem cells (HSCs), rare primitive cells capable of reconstituting all blood cell lineages, are the only stem cells currently routinely used for therapeutic purposes. Clinical experience has shown that HSC number is an important limiting factor in treatment success. Strategies to expand HSCs are of great clinical appeal, as they would improve therapeutic use of these cells in stem cell transplantation and in conditions of bone marrow failure. The microenvironment in which HSCs reside, known as the niche, has long been considered a critical regulator of HSCs. Data accumulated over the past decade strongly confirm the importance of the niche in HSC behavior. A number of niche components as well as signaling pathways, such as Notch, have been implicated in the interaction of the microenvironment with HSCs and continue to be genetically evaluated in the hope of defining the critical elements that are required and which, if modified, can initiate HSC behaviors. In this review, we highlight the known characteristics of HSCs, challenges in their expansion, the niche phenomenon, and explain why niche stimulated HSC expansion is of utmost interest in the field, while beginning to bring to the fore potential caveats of niche manipulation. Lastly, the potential pitfalls of avoiding malignancy and controlling self-renewal versus differentiation will be briefly reviewed.
造血干细胞（HSCs）是一种稀有原始细胞，能够重建所有血细胞谱系，是目前临床上常规用于治疗目的的唯一干细胞。临床经验表明，HSC 数量是治疗成功的一个重要限制因素。HSC 扩增策略具有重要的临床吸引力，因为它们将提高这些细胞在干细胞移植和骨髓衰竭情况下的治疗用途。造血干细胞所在的微环境，称为龛，长期以来一直被认为是 HSCs 的关键调节者。过去十年积累的数据强烈证实了微环境对 HSCs 行为的重要性。许多龛成分以及信号通路，如 Notch，已被牵连到微环境与 HSCs 的相互作用中，并继续在遗传上进行评估，希望确定所需的关键要素，如果加以修改，就可以启动 HSC 行为。在这篇综述中，我们强调了 HSCs 的已知特征、其扩增的挑战、龛现象，并解释了为什么龛刺激 HSC 扩增在该领域具有极大的兴趣，同时开始强调龛操作的潜在注意事项。最后，简要回顾了避免恶性肿瘤和控制自我更新与分化的潜在陷阱。
