Arachidonic acid and Docosahexanoic acid enhance platelet formation from human apheresis-derived CD34+ cells
Arachidonic acid and Docosahexanoic acid enhance platelet formation from human apheresis-derived CD34+ cells
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DOI：
10.1080/15384101.2017.1312233
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发表时间：
2017-01-01
期刊：
影响因子：
4.3
通讯作者：
Limaye, Lalita
中科院分区：
文献类型：
--
作者：
Dhenge, Ankita;Limbkar, Kedar;Limaye, Lalita
巨核细胞生成和血小板生成的异常是维持止血的两个重要过程，会导致血小板减少。尽管血小板输注被用来治疗这种疾病，但血库经常面临血小板短缺的问题。因此，大规模产生血小板的方法是非常可取的。然而，为了产生足够数量的巨核细胞(MK)和血小板(PLT)用于临床应用，了解血小板产生的机制并探索相应的有效策略是至关重要的。我们已报道N-6和N-3多不饱和脂肪酸(PUFAs)、花生四烯酸(AA)/二十二碳六酸(DHA)对脐带血CD34(+)细胞产生巨噬细胞集落刺激因子(MKs)和血小板(PLT)有促进作用。在这里，我们测试了外周血来源的CD34(+)细胞是否也有类似的效果，这种细胞在移植环境中更常用。我们发现，在PLT生物发生过程中，暴露于AA/DHA的细胞数量、表面标记表达、细胞倍体和细胞骨架成分的表达显著高于未暴露于这些多不饱和脂肪酸的对照细胞。测试细胞在NOD/SCID小鼠体内的植入效率高于对照细胞。AA/DHA似乎通过上调缺口和AKT通路促进了MK/PLT的生成。我们的数据表明，多不饱和脂肪酸在大规模生产临床应用的血小板的培养系统中可能是有价值的添加剂。
An Aberration in megakaryopoiesis and thrombopoiesis, 2 important processes that maintain hemostasis, leads to thrombocytopenia. Though platelet transfusions are used to treat this condition, blood banks frequently face a shortage of platelets. Therefore, methods to generate platelets on a large scale are strongly desirable. However, to generate megakaryocytes (MKs) and platelets (PLTs) in numbers sufficient for clinical application, it is essential to understand the mechanism of platelet production and explore efficient strategies accordingly. We have earlier reported that the N-6 and N-3 poly-unsaturated fatty acids (PUFAs), Arachidonic acid (AA)/Docosahexanoic acid (DHA) have beneficial effect on the generation of MKs and PLTs from umbilical cord blood derived CD34(+) cells. Here we tested if a similar effect is observed with peripheral blood derived CD34(+) cells, which are more commonly used in transplantation settings. We found a significant enhancement in cell numbers, surface marker expression, cellular ploidy and expression of cytoskeletal components during PLT biogenesis in cultures exposed to media containing AA/DHA than control cultures that were not exposed to these PUFAs. The test cells engrafted more efficiently in NOD/SCID mice than control cells. AA/DHA appears to have enhanced MK/PLT generation through upregulation of the NOTCH and AKT pathways. Our data show that PUFAs could be valuable additives in the culture system for large scale production of platelets for clinical applications.