N-acetyl-L-cysteine improves mesenchymal stem cell function in prolonged isolated thrombocytopenia post-allotransplant
N-acetyl-L-cysteine improves mesenchymal stem cell function in prolonged isolated thrombocytopenia post-allotransplant
复制标题
N-乙酰-L-半胱氨酸改善同种异体移植后长期孤立性血小板减少症的间充质干细胞功能
DOI：
10.1111/bjh.15119
复制
发表时间：
2018-03-01
影响因子：
6.5
通讯作者：
Huang, Xiao-Jun
中科院分区：
文献类型：
--
作者：
Kong, Yuan;Song, Yang;Huang, Xiao-Jun
长期孤立性血小板减少症（PT）是同种异体造血干细胞移植（alloo - hsct）的严重并发症。小鼠研究和体外实验表明，间充质干细胞（MSCs）不仅可以支持造血，还可以优先支持骨髓（BM）中的巨核细胞生成（megakyocytopogenesis）。然而，对于骨髓间充质干细胞在PT患者中的数量和功能知之甚少。在一项病例对照研究中，我们发现来自PT患者的骨髓间充质干细胞的增殖能力显著降低，活性氧增加，衰老。体外抗氧化剂（n-乙酰- l-半胱氨酸，NAC）处理不仅通过下调p38（也称为MAPK14）和p53（也称为TP53）通路，在数量和功能上改善了来自PT患者的骨髓间充质干细胞，而且还部分恢复了骨髓间充质干细胞支持巨核细胞生成的受损能力。随后，一项试点研究显示，7例入组PT患者（N=10）获得NAC治疗的总体缓解，无明显副作用。综上所述，结果表明功能失调的骨髓间充质干细胞在PT的发病机制中发挥了作用，体外NAC可以改善受损的骨髓间充质干细胞。虽然需要进一步验证，但我们的数据表明NAC可能是同种异体移植后PT患者的潜在治疗方法。
Prolonged isolated thrombocytopenia (PT) is a serious complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT). Murine studies and in vitro experiments suggest that mesenchymal stem cells (MSCs) can, not only to support haematopoiesis, but also preferentially support megakaryocytopoiesis in bone marrow (BM). However, little is known about the quantity and function of BM MSCs in PT patients. In a case-control study, we found that BM MSCs from PT patients exhibited significantly reduced proliferative capacities, increased reactive oxygen species and senescence. Antioxidant (N-acetyl-L-cysteine, NAC) treatment in vitro not only quantitatively and functionally improved BM MSCs derived from PT patients through down-regulation of the p38 (also termed MAPK14) and p53 (also termed TP53) pathways but also partially rescued the impaired ability of BM MSCs to support megakaryocytopoiesis. Subsequently, a pilot study showed that the overall response of NAC treatment was obtained in 7 of the enrolled PT patients (N=10) without significant side effects. Taken together, the results indicated that dysfunctional BM MSCs played a role in the pathogenesis of PT and the impaired BM MSCs could be improved by NAC invitro. Although requiring further validation, our data indicate that NAC might be a potential therapeutic approach for PT patients after allo-HSCT.