Haematologica. 2013 Dec;98(12):1964-71. doi: 10.3324/haematol.2013.086744. Epub 2013 Sep 13.
Patients who have undergone autologous stem cell transplantation are subsequently more susceptible to chemotherapy-induced bone marrow toxicity. In the present study, bone marrow primitive progenitor cells were examined one year after autologous stem cell transplantation and compared with normal bone marrow and mobilized peripheral blood stem cells. Post-transplantation bone marrow contained a significantly lower percentage of quiescent cells in the CD34(+)/CD38(low) fraction compared to normal bone marrow. In addition, we observed a strong decrease in stem cell/primitive progenitor frequency in post-transplantation CD34(+) cells as defined by long-term culture assays. Measurement of the levels of reactive oxygen species by flow cytometry revealed comparable levels in post-transplantation and normal bone marrow CD34(+)/CD38(low) cells, while significantly higher levels of reactive oxygen species were observed in CD34(+)/CD38(high) cells following autologous stem cell transplantation compared to normal bone marrow. Moreover, post-transplantation CD34(+) bone marrow cells demonstrated an increased sensitivity to buthionine sulfoximine, a trigger for endogenous production of reactive oxygen species. Gene expression analysis on CD34(+) cells revealed a set of 195 genes, including HMOX1, EGR1, FOS and SIRPA that are persistently down-regulated in mobilized peripheral blood cells and post-transplantation bone marrow compared to normal bone marrow. In conclusion, our data indicate that the diminished regenerative capacity of bone marrow following autologous stem cell transplantation is possibly related to a loss of quiescence and a reduced tolerability to oxidative stress.
接受自体干细胞移植的患者随后更容易受到化疗引起的骨髓毒性的影响。在本研究中，我们检查了自体干细胞移植一年后的骨髓原始祖细胞，并将其与正常骨髓和动员外周血干细胞进行了比较。与正常骨髓相比，移植后骨髓中 CD34(+) / CD38(low) 细胞群中的静止细胞比例显著降低。此外，我们观察到，长期培养试验中，移植后 CD34(+) 细胞中的干细胞/原始祖细胞频率明显降低。通过流式细胞术测量活性氧水平表明，移植后和正常骨髓 CD34(+) / CD38(low) 细胞中的活性氧水平相当，而与正常骨髓相比，自体干细胞移植后 CD34(+) / CD38(high) 细胞中的活性氧水平显著升高。此外，移植后 CD34(+) 骨髓细胞对丁硫氨酸亚砜亚胺表现出更高的敏感性，丁硫氨酸亚砜亚胺是内源性产生活性氧的触发剂。对 CD34(+) 细胞的基因表达分析显示，一组 195 个基因，包括 HMOX1、EGR1、FOS 和 SIRPA，在动员的外周血细胞和移植后骨髓中与正常骨髓相比持续下调。总之，我们的数据表明，自体干细胞移植后骨髓再生能力的减弱可能与静止状态的丧失和对氧化应激的耐受性降低有关。
