Chemical and Biological Engineering Department, Northwestern University, Evanston, IL 60208, USA.
Blood Cells Mol Dis. 2013 Mar;50(3):171-6. doi: 10.1016/j.bcmd.2012.11.007. Epub 2012 Dec 21.
Elucidating ways to enhance megakaryopoiesis in vivo would have therapeutic applications for thrombocytopenia and transfusion medicine. Nicotinamide has been shown to enhance endomitosis in megakaryocytes cultured in vitro, suggesting that it may be beneficial for the production of platelets in culture. We hypothesized that regular injections of nicotinamide in mice would also increase platelets in vivo. However, we found that platelet counts were reduced by about 25% with daily injections of nicotinamide. Altering the schedule, duration, or nicotinamide dose did not improve platelet production. Consistent with lower platelet levels, nicotinamide also tended to decrease megakaryocyte frequency in sternum and spleen sections, as well as colony formation in vitro by bone marrow progenitor cells. However, there was no effect on the fraction or ploidy of CD41(+) cells harvested from bone marrow. Together, our results suggest that, although nicotinamide increases polyploidization of megakaryocytes in culture, it does not have translatable effects in vivo.
阐明在体内增强巨核细胞生成的方法将对血小板减少症和输血医学具有治疗应用价值。烟酰胺已被证明可增强体外培养的巨核细胞中的核内有丝分裂,这表明它可能有益于培养中的血小板生成。我们假设在小鼠中定期注射烟酰胺也会增加体内的血小板。然而,我们发现每天注射烟酰胺会使血小板计数降低约 25%。改变方案、持续时间或烟酰胺剂量并不能改善血小板生成。与较低的血小板水平一致,烟酰胺也倾向于降低胸骨和脾脏切片中的巨核细胞频率,以及骨髓祖细胞在体外形成集落。然而,对从骨髓中收获的 CD41(+)细胞的分数或倍性没有影响。总之,我们的结果表明,尽管烟酰胺可增加巨核细胞在培养中的多倍性,但它在体内没有可转化的作用。