An Ning, Chen Yaozhen, Yin Dandan, Zhang Hui-Jie, Liu Zheng, Feng Fan, Li Na, Xin Jiajia, Yin Wen, Xu Xueqing, Hu Xingbin
1 Department of Transfusion Medicine, Xijing Hospital, The Fourth Military Medical University , Xi'an, China .
2 Department of Hematology, Tangdu Hospital, The Fourth Military Medical University , Xi'an, China .
Stem Cells Dev. 2017 Apr 1;26(7):495-502. doi: 10.1089/scd.2016.0139. Epub 2017 Feb 7.
The intrinsic basis of cancer-related anemia (CRA) is erythropoiesis disorder, which is a common complication of cancer and exerts a negative influence on the life quality of cancer patients. Cell therapy using mesenchymal stromal cells (MSCs) is considered as a promising method in cancer treatment. Furthermore, MSCs have been used to cure few type of anemia and be considered as a potential strategy to recover anemia radically. However, none reports its application in CRA treatment. In CRA model mice, we found that the number of linc-kitSca-1 and Sca-1 MSCs was decreased. And CRA resulted in an increased number of proerythroblasts and basophilic erythroblasts and decreased number of orthochromatic erythroblasts. Furthermore, in CRA model mice transplanted with Sca-1 MSCs and MSCs, the levels of red blood cell count and Hb in peripheral blood were obviously increased. And the accumulation of proerythroblasts and basophilic erythroblasts was inhibited. In addition, the expression patterns of GATA-1 and GATA-2, which is pivotal to anemia, were remarkably recovered. Our results demonstrated that either MSCs or its subpopulation could effectively recover CRA erythropoiesis through GATA-1/GATA-2 signaling, which outstrips the traditional symptomatic therapy.
癌症相关性贫血（CRA）的内在基础是红细胞生成紊乱，这是癌症的常见并发症，对癌症患者的生活质量产生负面影响。使用间充质基质细胞（MSC）的细胞疗法被认为是癌症治疗中有前景的方法。此外，MSC已被用于治疗少数类型的贫血，并被视为从根本上恢复贫血的潜在策略。然而，尚无关于其在CRA治疗中应用的报道。在CRA模型小鼠中，我们发现linc-kitSca-1和Sca-1 MSC的数量减少。并且CRA导致早幼红细胞和嗜碱性成红细胞数量增加，正染性成红细胞数量减少。此外，在移植了Sca-1 MSC和MSC的CRA模型小鼠中，外周血红细胞计数和血红蛋白水平明显升高。并且早幼红细胞和嗜碱性成红细胞的积累受到抑制。此外，对贫血起关键作用的GATA-1和GATA-2的表达模式明显恢复。我们的结果表明，MSC或其亚群均可通过GATA-1/GATA-2信号传导有效恢复CRA的红细胞生成，这优于传统的对症治疗。
