Pre-activation of mesenchymal stem cells with TNF-α, IL-1β and nitric oxide enhances its paracrine effects on radiation-induced intestinal injury.
Pre-activation of mesenchymal stem cells with TNF-α, IL-1β and nitric oxide enhances its paracrine effects on radiation-induced intestinal injury.
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用 TNF-α、IL-1β 和一氧化氮预激活间充质干细胞增强其对辐射引起的肠道损伤的旁分泌作用
DOI：
10.1038/srep08718
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发表时间：
2015-03-03
影响因子：
4.6
通讯作者：
Chen QK
中科院分区：
文献类型：
--
作者：
Chen H;Min XH;Wang QY;Leung FW;Shi L;Zhou Y;Yu T;Wang CM;An G;Sha WH;Chen QK
间充质干细胞条件培养基（MSC-CM）可能是 MSC 移植的一种有前途的替代品，然而，非活化 MSC-CM 中生长因子浓度低阻碍了其临床应用。最近的数据表明，炎症因子可以增强间充质干细胞的旁分泌潜力。在此，我们在辐射诱导炎症条件下预激活骨髓来源的间充质干细胞（MSCIEC-6（IR）），并研究MSC-CMIEC-6（IR）和非激活的MSC-CM对辐射诱导的肠损伤（RIII）的不同作用的证据和机制。全身输注 MSC-CMIEC-6(IR)，而非未激活的 MSC-CM，可显着改善受辐射大鼠的肠道损伤和存活率。这些益处可能涉及上皮再生和炎症的调节，如肠上皮/干细胞的再生、促炎/抗炎细胞因子平衡的调节所表明的。 MSCIEC-6(IR) 卓越的旁分泌功效的机制与再生、免疫调节和运输分子的更高分泌有关，包括关键因子 IGF-1，由 TNF-α、IL-1β 和一氧化氮部分通过血红素加氧酶-1 依赖性机制诱导。总之，我们的研究结果表明，用 TNF-α、IL-1β 和一氧化氮预激活 MSC，可通过血红素加氧酶 1 依赖性机制增强其对 RIII 的旁分泌作用，这可能有助于我们最大限度地发挥 MSC 的旁分泌潜力。
Conditioned medium from mesenchymal stem cells (MSC-CM) may represent a promising alternative to MSCs transplantation, however, the low concentrations of growth factors in non-activated MSC-CM hamper its clinical application. Recent data indicated that the paracrine potential of MSCs could be enhanced by inflammatory factors. Herein, we pre-activated bone-marrow-derived MSCs under radiation-induced inflammatory condition (MSCIEC-6(IR)) and investigated the evidence and mechanism for the differential effects of MSC-CMIEC-6(IR)and non-activated MSC-CM on radiation-induced intestinal injury (RIII). Systemic infusion of MSC-CMIEC-6(IR), but not non-activated MSC-CM, dramatically improved intestinal damage and survival of irradiated rats. Such benefits may involve the modulation of epithelial regeneration and inflammation, as indicated by the regeneration of intestinal epithelial/stem cells, the regulation of the pro-/anti-inflammatory cytokine balance. The mechanism for the superior paracrine efficacy of MSCIEC-6(IR)is related to a higher secretion of regenerative, immunomodulatory and trafficking molecules, including the pivotal factor IGF-1, induced by TNF-α, IL-1β and nitric oxide partially via a heme oxygenase-1 dependent mechanism. Together, our findings suggest that pre-activation of MSCs with TNF-α, IL-1β and nitric oxide enhances its paracine effects on RIII via a heme oxygenase-1 dependent mechanism, which may help us to maximize the paracrine potential of MSCs.
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