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脂肪来源的间充质干细胞(ADSCs)在辐射诱导的血小板减少小鼠模型中具有改善血小板恢复、增强巨核细胞生成和抑制骨髓细胞凋亡的潜力。

Adipose-Derived Mesenchymal Stem Cells (ADSCs) With the Potential to Ameliorate Platelet Recovery, Enhance Megakaryopoiesis, and Inhibit Apoptosis of Bone Marrow Cells in a Mouse Model of Radiation-Induced Thrombocytopenia.

作者信息

Zhang Jiamin, Zhou Shiyuan, Zhou Yi, Feng Feier, Wang Qianming, Zhu Xiaolu, Zhao Jingzhong, Fu Haixia, Lv Meng, Ai Huisheng, Huang Xiaojun, Zhang Xiaohui

机构信息

Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.

出版信息

Cell Transplant. 2016;25(2):261-73. doi: 10.3727/096368915X688155. Epub 2015 May 13.

Abstract

Substantial damage to the bone marrow can be caused by exposure to radiation, which can then develop into severe thrombocytopenia. In this study, we investigated the in vivo impact of adipose-derived mesenchymal stem cells (ADSCs) on megakaryopoiesis and platelet recovery in irradiated mice. Radiation markedly reduced peripheral blood counts. Recovery of both platelets and WBCs was better in the ADSC-treated group compared with the saline group and the fibroblast group 21 days after irradiation. A significant increase in the total CFU and MK-CFU after irradiation was observed in the ADSC group compared with the saline group and the fibroblast group. Further, the proportion of CD41(+) cells in the ADSC group was significantly higher than that in the saline group and the fibroblast group. ADSC treatment significantly improved the cellularity and decreased the apoptotic cells in the bone marrow while normal fibroblasts did not. Administration of ADSCs upregulated protein expression of phosphorylated Akt and Bcl-xL, whereas the expression of Bax, a protein related to apoptosis, was significantly lower in the ADSC group. In conclusion, this study suggests that ADSCs were capable of promoting platelet recovery, improving megakaryopoiesis, and inhibiting apoptosis of bone marrow cells in irradiated mice. The antiapoptotic effect of ADSCs is likely to be mediated via the PI3K/Akt pathway. These findings may provide a scientific basis for using ADSCs as a new therapy after irradiation.

摘要

暴露于辐射可对骨髓造成严重损伤,进而发展为严重的血小板减少症。在本研究中,我们调查了脂肪来源的间充质干细胞(ADSCs)对受辐照小鼠巨核细胞生成和血小板恢复的体内影响。辐射显著降低了外周血计数。与生理盐水组和成纤维细胞组相比,ADSC治疗组在辐照后21天血小板和白细胞的恢复情况更好。与生理盐水组和成纤维细胞组相比,ADSC组辐照后总集落形成单位(CFU)和巨核细胞集落形成单位(MK-CFU)显著增加。此外,ADSC组中CD41(+)细胞的比例显著高于生理盐水组和成纤维细胞组。ADSC治疗显著改善了骨髓细胞密度并减少了凋亡细胞,而正常成纤维细胞则没有。给予ADSCs上调了磷酸化Akt和Bcl-xL的蛋白表达,而与凋亡相关的蛋白Bax在ADSC组中的表达显著较低。总之,本研究表明ADSCs能够促进受辐照小鼠的血小板恢复,改善巨核细胞生成,并抑制骨髓细胞凋亡。ADSCs的抗凋亡作用可能是通过PI3K/Akt途径介导的。这些发现可能为将ADSCs用作辐照后的新疗法提供科学依据。

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