Ballen K
Division of Hematology/Oncology, Massachusetts General Hospital, Boston, MA 02214, USA.
Bone Marrow Transplant. 2007 Jun;39(11):655-60. doi: 10.1038/sj.bmt.1705651. Epub 2007 Apr 2.
During human development, stem cells establish themselves in specific anatomic locations or niches. The niche harbors the stem cells, and regulates how stem cells proliferate. The interaction between stem cells and their niche affects stem cell function, and offers an opportunity to improve the marrow microenvironment. Osteoblasts produce hematopoietic growth factors and are activated by parathyroid hormone (PTH). A calcium sensing receptor, expressed by hematopoietic stem cells, regulates the niche and can be targeted to increase stem cell numbers. Therefore, drugs that affect osteoblast function or target calcium receptors may be useful for stem cell mobilization and engraftment. In this review, the biology of the stem cell niche and the potential therapeutic manipulations of the stem cell niche are reviewed. PTH is in clinical trials for patients who have not mobilized autologous stem cells well. The limiting cell numbers for adult cord blood transplantation increase the risk of infection, and PTH is currently in a clinical trial following cord blood transplantation in an effort to improve engraftment and immune reconstitution.
在人类发育过程中，干细胞定位于特定的解剖位置或微环境中。微环境容纳干细胞，并调节干细胞的增殖。干细胞与其微环境之间的相互作用影响干细胞功能，并为改善骨髓微环境提供了契机。成骨细胞产生造血生长因子，并被甲状旁腺激素（PTH）激活。造血干细胞表达的钙敏感受体调节微环境，并且可以作为靶点来增加干细胞数量。因此，影响成骨细胞功能或靶向钙受体的药物可能有助于干细胞的动员和植入。在本综述中，我们回顾了干细胞微环境的生物学特性以及对干细胞微环境的潜在治疗性操作。PTH正在用于自体干细胞动员效果不佳患者的临床试验中。成人脐血移植中有限的细胞数量增加了感染风险，目前PTH正在脐血移植后的临床试验中，以努力改善植入和免疫重建。
