A novel study on the immunomodulatory effect of umbilical cord derived mesenchymal stem cells pretreated with traditional Chinese medicine Asarinin
A novel study on the immunomodulatory effect of umbilical cord derived mesenchymal stem cells pretreated with traditional Chinese medicine Asarinin
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中药细辛素预处理脐带间充质干细胞免疫调节作用的新研究
DOI：
10.1016/j.intimp.2021.108054
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发表时间：
2021-09-03
影响因子：
5.6
通讯作者：
Ling, Xiaosui
中科院分区：
文献类型：
--
作者：
He, Haiping;Yang, Tonghua;Ling, Xiaosui
同种异体造血干细胞移植（HSCT）仍然是恶性血液病治疗的关键，而同种异体移植后可能发生的急性移植物抗宿主病（aGVHD）可危及生命并促进疾病复发。GVHD通过上调T辅助1细胞因子（Th1）细胞因子和刺激CD4？CD8 + T细胞。GVHD具有显著的免疫调节作用，但易受间充质干细胞（mesenchymal stem cells， MSC）环境的影响，因此间充质干细胞对GVHD的免疫抑制作用尚不明确。因此，为了更好地了解间充质干细胞在GVHD预防和治疗中的作用，我们对脐带源性间充质干细胞（UC-MSC）进行了中药细沙蒿素和ifn - γ预处理。在混合淋巴细胞反应中，我们发现Asarinin预处理的UC-MSC对aGVHD小鼠模型CD4和CD8 + T细胞增殖的抑制作用明显增强，下调Th1型细胞因子，上调Th2型细胞因子，减轻肝、肺、肠的炎症损伤。此外，细辛素可与ifn - γ协同促进UC-MSC分泌吲哚胺2,3-双加氧酶（IDO）。我们的研究结果表明，Asarinin预处理的UC-MSC可以显著促进MSC对造血干细胞移植后aGVHD的免疫抑制作用。
Allogeneic hematopoietic stem cell transplantation (HSCT) remains the key for the treatment of malignant hematological diseases, and acute graft-versus-host disease (aGVHD) that might occur after allogenic transplantation can be life threatening and promote disease recurrence. GVHD damages the various parts of the body by upregulating T helper 1 cytokines (Th1) cytokines and stimulating CD4?CD8 + T cells. GVHD can exhibit significant immunoregulatory effects, but could be easily affected by the mesenchymal stem cells (MSC) environment, and hence the MSC immunosuppressive effects on GVHD remain unpredictable. Hence, to better understand the role of MSC in the prevention and treatment of GVHD, umbilical cord derived mesenchymal stem cells (UC-MSC) were pretreated with Chinese medicine Asarinin and IFN-gamma. In the mix lymphocyte reaction, we found that Asarinin pretreated UC-MSC can exert significantly greater inhibition towards the proliferation of CD4 and CD8 + T cells, down-regulate Th1 type cytokines, up-regulate Th2 type cytokines, and reduce the inflammatory damage to liver, lung and intestine of aGVHD mice model. Moreover, Asarinin can cooperate with IFN-gamma to promote UC-MSC to secrete indoleamine 2,3-dioxygenase (IDO). Our findings establish that Asarinin pre-treated UC-MSC can significantly promote the immunosuppressive effects of MSC on aGVHD after hematopoietic stem cell transplantation.