Adams G B, Scadden D T
Center for Stem Cell and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Gene Ther. 2008 Jan;15(2):96-9. doi: 10.1038/sj.gt.3303063. Epub 2007 Nov 15.
The success of hematopoietic stem cell (HSC)-based therapies relies on the ability of the stem cells to both engraft and self-renew sufficiently in the bone marrow microenvironment. Previous studies identified that a number of components of bone contribute to the regulation of HSCs indicating that they participate in a stem cell 'niche'. This niche is a dynamic microenvironment that changes during development and with varying physiologic states. Components of it, such as the osteoblast, can be modulated through pharmacological treatment. Reasoning that the stem cell niche may be manipulated to augment the effectiveness of stem cell therapies, we demonstrated that daily treatment with parathyroid hormone (a clinically approved method for increasing osteoblast function) resulted in therapeutic benefit in three clinically relevant models of stem cell therapy. These results suggest that the niche may be a pharmacological target for altering stem cell function in settings of regenerative medicine.
基于造血干细胞（HSC）的疗法的成功依赖于干细胞在骨髓微环境中充分植入并自我更新的能力。先前的研究表明，骨骼的许多成分有助于调节造血干细胞，这表明它们参与了干细胞“龛”的形成。这个龛是一个动态的微环境，在发育过程中以及不同的生理状态下会发生变化。其组成部分，如成骨细胞，可以通过药物治疗进行调节。考虑到干细胞龛可能被操控以增强干细胞疗法的效果，我们证明，在三种临床相关的干细胞治疗模型中，每日使用甲状旁腺激素治疗（一种临床上认可的增强成骨细胞功能的方法）产生了治疗益处。这些结果表明，在再生医学领域，龛可能是改变干细胞功能的一个药理学靶点。
