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Blood:诱导脂肪间充质干细胞分化成血小板有望缓解临床血小板输注需求压力

2018-12-02 MedSci MedSci原创

临床对输血小板的需求正在增加。但是,供体依赖性的血小板输注存在很多实际问题,如供应有限和感染风险。Keiichi Tozawa等人尝试开发不依赖于供细胞来源的血小板的制造系统,即人类脂肪间充质基质/干细胞系(ASCL)。采用倒置培养瓶法可获得ASCL。ASCL满足国际细胞治疗学会所定义的间充质干细胞(MSC)的最低标准。ASCL的增殖能力至少可维持2个月,且无任何异常核型。可采用巨核细胞诱导型培养

临床对输血小板的需求正在增加。但是,供体依赖性的血小板输注存在很多实际问题,如供应有限和感染风险。Keiichi Tozawa等人尝试开发不依赖于供细胞来源的血小板的制造系统,即人类脂肪间充质基质/干细胞系(ASCL)。

采用倒置培养瓶法可获得ASCL。ASCL满足国际细胞治疗学会所定义的间充质干细胞(MSC)的最低标准。ASCL的增殖能力至少可维持2个月,且无任何异常核型。可采用巨核细胞诱导型培养基培养ASCL。培养的第12天,获得的ASCL来源的血小板(ASCL-PLT)达到峰值。

研究人员发现CD42b阳性细胞表达一种与细胞黏附相关的MSC标志物——CD90。与外周血小板相比,ASCL-PLT表现出更高水平的PAC1结合、P-选择素表面暴露、瑞斯西丁素诱导性血小板聚集和ADP诱导性血小板聚集;而纤维素原结合和胶原蛋白诱导性血小板聚集水平相似。ASCL-PLT的肾上腺素诱导性血小板聚集较低。ASCL-PLT输注到放射厚度免疫缺陷的NSG小鼠后的体内动力学模式与输注浓缩血小板的相似。

ASCL-PLT除了具有其他血小板所具有的特征之外,可能还额外具有MSC的功能。无论是建立ASCL还是诱导分化ASCL-PLT均不需要基因转导,仅采用内源性血栓生成素即可诱导分化。该诱导方案简单易行,不需要饲养层细胞,有利于推广该方案的临床应用。


原始出处:

Keiichi Tozawa, et al. Unique megakaryocytes and platelets from novel human adipose-derived mesenchymal stem cell line. Blood  2018  :blood-2018-04-842641;  doi: https://doi.org/10.1182/blood-2018-04-842641

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