Human mesenchymal stem cells modulate B-cell functions
Human mesenchymal stem cells modulate B-cell functions
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DOI：
10.1182/blood-2005-07-2657
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发表时间：
2006-01-01
期刊：
影响因子：
20.3
通讯作者：
Uccelli, A
中科院分区：
文献类型：
--
作者：
Corcione, A;Benvenuto, F;Uccelli, A
人骨髓间充质干细胞(HMSCs)抑制T细胞和树突状细胞的功能，为自身免疫性疾病的细胞治疗提供了一种很有前途的策略。然而，目前还没有关于hMSCs对B细胞的影响的信息，这可能会对这些细胞的临床应用产生很大影响。从健康供者的骨髓中分离hMSCs和从外周血中分离纯化的B细胞，与不同的B细胞趋化刺激共培养。HMSCs通过阻滞细胞周期的G(0)/G(1)期抑制B细胞的增殖，而不是通过诱导细胞凋亡。Transwell实验表明，抑制B细胞的主要机制是hMSC产生可溶性因子。HMSCs抑制B细胞分化，因为IgM、Ig G和Ig A的产生明显受损。HMSCs显著下调CXCR4、CXCR5和CCR7B细胞的表达，以及对CXCR4配体CXCL12和CXCR5配体CXCL13的趋化作用，提示这些细胞影响B细胞的趋化特性。HMSCs不影响B细胞共刺激分子的表达和细胞因子的产生。这些结果进一步支持了hMSCs在免疫介导性疾病中的潜在治疗用途，包括B细胞在其中发挥主要作用的疾病。
Human mesenchymal stem cells (hMSCs) suppress T-cell and dendritic-cell function and represent a promising strategy for cell therapy of autoimmune diseases. Nevertheless, no information is currently available on the effects of hMSCs on B cells, which may have a large impact on the clinical use of these cells. hMSCs isolated from the bone marrow and B cells purified from the peripheral blood of healthy donors were cocultured with different B-cell tropic stimuli. B-cell proliferation was inhibited by hMSCs through an arrest in the G(0)/G(1) phase of the cell cycle and not through the induction of apoptosis. A major mechanism of B-cell suppression was hMSC production of soluble factors, as indicated by transwell experiments. hMSCs inhibited B-cell differentiation because IgM, IgG, and IgA production was significantly impaired. CXCR4, CXCR5, and CCR7 B-cell expression, as well as chemotaxis to CXCL12, the CXCR4 ligand, and CXCL13, the CXCR5 ligand, were significantly down-regulated by hMSCs, suggesting that these cells affect chemotactic properties of B cells. B-cell costimulatory molecule expression and cytokine production were unaffected by hMSCs. These results further support the potential therapeutic use of hMSCs in immune-mediated disorders, including those in which B cells play a major role.