Human mesenchymal stromal cells attenuate graft-versus-host disease and maintain graft-versus-leukemia activity following experimental allogeneic bone marrow transplantation.
Human mesenchymal stromal cells attenuate graft-versus-host disease and maintain graft-versus-leukemia activity following experimental allogeneic bone marrow transplantation.
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DOI：
10.1002/stem.1867
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发表时间：
2015-02
期刊：
影响因子：
5.2
通讯作者：
Cooke, Kenneth R.
中科院分区：
文献类型：
--
作者：
Auletta, Jeffery J.;Eid, Saada K.;Wuttisarnwattana, Patiwet;Silva, Ines;Metheny, Leland;Keller, Matthew D.;Guardia-Wolff, Rocio;Liu, Chen;Wang, Fangjing;Bowen, Theodore;Lee, Zhenghong;Solchaga, Luis A.;Ganguly, Sudipto;Tyler, Megan;Wilson, David L.;Cooke, Kenneth R.
我们试图确定人骨髓间充质干细胞（hMSCs）对移植物抗宿主病（GvHD）和移植物抗白血病（GvL）活性的影响和潜在机制。给予C57 BL/6 BM和脾T细胞并用hMSC处理的辐照B6 D2 F1小鼠具有降低的全身GvHD、供体T细胞扩增以及血清TNFα和IFNγ水平。生物发光成像表明，hMSC重新分配从肺部到腹部器官在72小时内，从hMSC治疗的异基因骨髓移植小鼠收获的靶组织有较少的GvHD比未经处理的对照组。冷冻成像更精确地揭示了hMSCs优先分布于脾边缘区，并调节白色髓中的T细胞扩增。重要的是，hMSC对体外细胞毒性T细胞活性没有影响，并在体内保留了有效的GvL效应。含有hMSCs的混合白细胞培养物显示T细胞增殖降低，TNFα、IFNγ和IL-10降低，但PGE 2水平升高。吲哚美辛和E-前列腺素2（EP 2）受体拮抗剂均逆转，而EP 2激动剂恢复了hMSC介导的体外T细胞抑制，证实了PGE 2的作用。此外，环氧化酶抑制后alloBMT废除了hMSCs的保护作用。总之，我们的数据表明，hMSC保留GvL活性和减弱GvHD，并揭示hMSC生物分布到次级淋巴器官，其中它们可能通过PGE 2诱导减弱同种异体反应性T细胞增殖。
We sought to define the effects and underlying mechanisms of human, marrow-derived mesenchymal stromal cells (hMSCs) on graft-versus-host disease (GvHD) and graft-versus-leukemia (GvL) activity. Irradiated B6D2F1 mice given C57BL/6 BM and splenic T-cells and treated with hMSCs had reduced systemic GvHD, donor T-cell expansion, and serum TNFα and IFNγ levels. Bioluminescence imaging demonstrated that hMSCs redistributed from lungs to abdominal organs within 72h; and target tissues harvested from hMSC-treated alloBMT mice had less GvHD than untreated controls. Cryo-imaging more precisely revealed that hMSCs preferentially distributed to splenic marginal zones and regulated T-cell expansion in the white pulp. Importantly, hMSCs had no effect on in vitro cytotoxic T-cell activity and preserved potent GvL effects in vivo. Mixed leukocyte cultures containing hMSCs exhibited decreased T-cell proliferation, reduced TNFα, IFNγ, and IL-10, but increased PGE2 levels. Indomethacin and E-prostanoid 2 (EP2) receptor antagonisms both reversed while EP2 agonism restored hMSC-mediated in vitro T-cell suppression, confirming the role for PGE2. Furthermore, cyclo-oxygenase inhibition following alloBMT abrogated the protective effects of hMSCs. Together, our data show that hMSCs preserve GvL activity and attenuate GvHD and reveal that hMSC biodistribute to secondary lymphoid organs wherein they attenuate alloreactive T-cell proliferation likely through PGE2 induction.
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影响因子：
4.3
作者：
Auletta JJ;Zale EA;Welter JF;Solchaga LA
通讯作者：
Solchaga LA
DOI：
10.1016/s1470-2045(13)70512-6
发表时间：
2014-01
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Choi SW;Braun T;Chang L;Ferrara JL;Pawarode A;Magenau JM;Hou G;Beumer JH;Levine JE;Goldstein S;Couriel DR;Stockerl-Goldstein K;Krijanovski OI;Kitko C;Yanik GA;Lehmann MH;Tawara I;Sun Y;Paczesny S;Mapara MY;Dinarello CA;DiPersio JF;Reddy P
通讯作者：
Reddy P
影响因子：
8.7
作者：
Fuchs EJ
通讯作者：
Fuchs EJ
影响因子：
20.3
作者：
Beilhack, A;Schulz, S;Negrin, RS
通讯作者：
Negrin, RS
影响因子：
4.6
作者：
English, K.;Ryan, J. M.;Mahon, B. P.
通讯作者：
Mahon, B. P.