Brouard Nathalie, Driessen Rebecca, Short Brenton, Simmons Paul J
Center for Stem Cell Research, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, 1825 Pressler Street, Houston, TX 77030, USA.
Stem Cell Res. 2010 Jul;5(1):65-75. doi: 10.1016/j.scr.2010.04.002. Epub 2010 Apr 21.
During the course of studies to investigate whether MPC circulate in response to G-CSF, the agent most frequently used to induce mobilization of hematopoietic progenitors, we observed that while G-CSF failed to increase the number of MPC in circulation (assayed in vitro as fibroblast colony-forming cells, CFU-F), G-CSF administration nevertheless resulted in a time-dependent increase in the absolute number of CFU-F within the BM, peaking at Day 7. Treatment of BM cells from G-CSF-treated mice with hydroxyurea did not alter CFU-F numbers, suggesting that the increase in their numbers in response to G-CSF administration is not due to proliferation of existing CFU-F. Given previous studies demonstrating that G-CSF potently induces bone turnover in mice, we hypothesized that the increase in CFU-F may be triggered by the bone resorption that occurs following G-CSF administration. In accord with this hypothesis, administration of an inhibitor of osteoclast differentiation, osteoprotegerin (OPG), prevented the increase of CFU-F numbers induced by G-CSF. In conclusion, these data indicate that the cytokine treatment routinely used to mobilize hematopoietic stem cells could provide a readily applicable method to induce in vivo expansion of MPC for clinical applications.
在研究粒细胞集落刺激因子（G-CSF，最常用于诱导造血祖细胞动员的因子）是否能促使多能祖细胞（MPC）循环的过程中，我们观察到，虽然G-CSF未能增加循环中MPC的数量（体外检测为成纤维细胞集落形成细胞，CFU-F），但G-CSF给药后，骨髓内CFU-F的绝对数量却随时间增加，并在第7天达到峰值。用羟基脲处理G-CSF处理小鼠的骨髓细胞，CFU-F数量未改变，这表明其数量因G-CSF给药而增加并非源于现有CFU-F的增殖。鉴于先前的研究表明G-CSF能有效诱导小鼠的骨转换，我们推测CFU-F数量的增加可能是由G-CSF给药后发生的骨吸收所触发。与此假设一致，给予破骨细胞分化抑制剂骨保护素（OPG）可阻止G-CSF诱导的CFU-F数量增加。总之，这些数据表明，常用于动员造血干细胞的细胞因子治疗可为临床应用诱导体内MPC扩增提供一种易于应用的方法。
